Lena Winestone, MD, Assistant Professor of Pediatrics, University of California, San Francisco

What have you found regarding how neighborhoods, specifically if they are those with low income and low education, impact survival in children with cancer?

We found that children with acute myeloid leukemia, a type of leukemia that aff ects children, have an increased risk of mortality if they come from a low-income or

high-poverty neighborhood. In particular, we looked at that and broke it down in several diff erent ways. We looked at the risk of relapse and found that there was an increased risk of relapse among those patients. And in addition, we found that they had a higher risk of toxicity that led to mortality among that patient  population. Finally, we looked at early mortality as a marker, potentially, of access to care, and found that low-income patients also have a substantial increased risk of

early mortality or death during the fi rst course of chemotherapy, suggesting that a component of what’s going on may be related to access.

Winestone LE, Getz KD, Bona KO, et al. Area-based socioeconomic disparities in survival of children with newly diagnosed acute myeloid leukemia: a report from the Children’s Oncology Group. Presented at: 61st—American Society of Hematology Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL. Abstract 703.–ash.confex.com/ash/2019/webprogram/Paper130978.html. Accessed December 21, 2019.

Michael Wang, MD, Professor, Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center

What were your findings of using ibrutinib as a frontline treatment in patients in mantle cell lymphoma (MCL), and how might these findings change treatment decision making for these patients?

A perfect example of the toxicities of chemotherapy is the Hyper-CVAD [cyclophosphamide, vincristine, doxorubicin and dexamethasone] chemotherapy. Hyper-CVAD has been used for young patients newly diagnosed with mantle cell lymphoma. [To receive] Hyper-CVAD, you have to be in the hospital for 7 days, and then every month for 8 cycles, therefore, 8 months; and [approximately] 20% of patients after 15 years will develop another cancer. So, in order to cut down this therapy, you cannot say, “Hey, Dr Wang, today I have ibrutinib and I don’t need Hyper-CVAD,” that’s not science. In science and clinical medicine, you cannot go from one extreme to the other extreme, you have to have a stepwise, gradual fashion. 

So, WINDOW-1 clinical trial was designed—and it [was] presented in a poster

—we used an ibrutinib chemo-free window&mdash;why’s it called a window, because before strictly heading to chemotherapy, we use rituximab-ibrutinib in the window period and we fi nd out, after we get a complete remission, then we can use the chemotherapy with only 50% of the original dosage? The WINDOW-1 [clinical trial] utilized the chemo-free therapy upfront with ibrutinib and rituximab; in this case, the response rate is nearly 100%. The CR [complete remission] rate is between 92% to 94%, and you can see it in my poster and in my abstract. And my God, this is very powerful. And then, after patients are already in CR, we given them 4 cycles of chemo consolidation.

This, so far, is very successful. I have presented these data many times. We think we made progress to cut down the chemotherapy by incorporating, in a rational way, the chemo-free therapy. And of course, you never want to stop—the WINDOW-2 trial, in addition to ibrutinib and rituximab, we added another chemo-free agent, called venetoclax, which is targeting BCL-2&mdash;very powerful. And with this we try to drive the overall response rate to 100%. And then, if the patient is low-risk, there will be no chemotherapy needed. High-risk … blastoid, big tumors, and complex karyotype, 4 cycles. Low-risk none, intermediate[-risk] only 2 cycles. You can see from WINDOW-1 to WINDOW-2, gradually we are reducing chemo and try to further improve efficacy and decrease mortality from the toxicities. So, it’s a very exciting time for chemo-free therapy. 

Wang ML, Jain P, Lee HJ, et al. Frontline treatment with ibrutinib plus rituximab (IR) followed by short course R-HyperCVAD/MTX is extremely potent and safe in patients (age ≤ 65 years) with mantle cell lymphoma (MCL)—results of phase-II WINDOW-1 clinical trial. Presented at: 61st American Society of Hematology Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL. Abstract 3987. ash.confex.com/ash/2019/webprogram/Paper126044.html. Accessed December 21, 2019.

C. Ola Landgren, MD, PhD, Professor of Medicine, Chief of Myeloma Service, Memorial Sloan Kettering Cancer Center 

Carfilzomib is currently approved to treat patients with relapsed or refractory multiple myeloma—what did you find regarding the safety and efficacy of

At [the 61st American Society of Hematology (ASH) Annual Meeting & Exposition] 2019, I’m the lead presenter, I’m the lead principal investigator for a phase 2 trial developed at [Memorial] Sloan Kettering, where we used the combination of carfi lzomib with lenalidomide, dexamethasone, and also daratumumab. This is a phase 2 trial targeting newly diagnosed multiple myeloma patients.

The cohort I present uses once a week dosing with carfi lzomib—it’s a so-called 20/56 mg per meter squared dosing. So, 20 mg per meter squared, the first dose, and every other dose after that 56 mg per meter squared. So, once a week on a 4-week schedule means day 1, day 8, and day 15. Daratumumab is given standard dosing per the FDA label, which is 16 mg/kg body weight and is given weekly for the fi rst 2 cycles and then is every other week for another 4 cycles. And the last cycles are once every 4 weeks. This phase 2 trial includes a total of 8 cycles of therapy. And the patient can go on [the trial], if they have a new diagnosis of myeloma, they fi t the standard eligibility criteria, and it doesn’t matter if they are younger or older, it doesn’t matter if they are transplant candidates or not. Because the study is designed to look at minimal residual disease (MRD) as the primary end point after 8 cycles.

In the current literature, the best published MRD rates are in the range of around 30% or 40% or so—in this study that’s not yet published, but presented

at the ASH 2019, we report MRD rate of around 80%, and this is without bone marrow transplantation.

Landgren O, Hultcrantz M, Lesokhin AM, et al. Weekly carfilzomib, lenalidomide, dexamethasone and daratumumab (wKRd-D) combination therapy provides unprecedented MRD negativity rates in newly diagnosed multiple myeloma: a clinical and correlative phase 2 study. Presented at: 61st¡American Society of Hematology Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL. Abstract 862. ash.confex.com/ash/2019/webprogram/Paper126378.html. Accessed December 21, 2019.

Lindsey Roeker, MD, Clinical Fellow, Memorial Sloan Kettering Cancer Center 

What are some of the real-world unknowns regarding treatment patterns in CLL [chronic lymphocytic leukemia]? 

Right now, we have basically prospective data showing the effi cacy of a lot of novel agents—which is fantastic. But how they work in sequences is still an unknown question. We have small numbers of patients that have been treated with a novel agent after a novel agent. So, venetoclax after ibrutinib, we know that works. But the converse, whether ibrutinib works after venetoclax, is still somewhat of a question. We have real-world data to support the use in people who have not previously been exposed to a BTK [Bruton tyrosine kinase] inhibitor, or for patients who have previously seen a BTK inhibitor but stopped because of intolerance. For patients who have actually previously failed a BTK inhibitor, it seems to be a less-eff ective strategy. 

But that’s all real-world data, retrospective. We don’t have a prospective, large data set to support that practice. So, I think that’s still a piece that we’re trying to figure out.

Adam Olszewski, MD, Associate Professor of Medicine, Warren Alpert Medical School, Brown University

Why is palliative care not used earlier for patients with hematologic malignancies?

This is a very interesting and complex and heavily researched issue, actually. There are many studies that show patients with hematologic malignancies receive less end-of-life, less appropriate end-of-life care. So, they are receiving much more aggressive end-of-life care. And it is very easy to theorize about this, how this is happening, that, you know, patients with blood cancers have, that are often hanging in this state, where further treatment is always possible and remission is always possible. And that makes it very diffi cult for patients and for clinicians to actually recognize the moment where palliative care should come in to help manage patients’ symptoms and maybe start thinking about really what are further goals of care and what the patient is expecting in terms of their realistic life expectancy.

A lot of research is showing that both clinicians have diffi culty with this and patients may have diffi culty with this as well. There’s some prognostic discordance between patients and clinicians when discussing the prognosis of patients with leukemias and lymphomas, and myelomas as well. And then clinicians often have that perception that private care was developed for management of solid tumors, and that the needs of blood cancer patients may not be met fully with what has been developed. I feel that palliative care physicians are actually quite prepared to manage blood cancer patients, although they also need additional training because approaching a patient, you know a young person with multiple relapsed lymphoma or leukemia is quite diff erent from often older patients with solid tumor that progressed as many lines of chemotherapy. 

So, I think there are barriers on the clinician side, on the patient side, and there are also some systemic barriers. The study, it was shown, during this  ASH, demonstrated that only a very, very small number of patients actually billed palliative care services early during the course of their disease—at least 30 days prior to their death. This was barely 2% even though it is increasing in the recent years.

But the difficulty that arises is also realization that the way we are billing and documenting these services is actually very diffi cult to capture later on through health services research. And that actually refl ects challenges with billing and arranging and putting on this layer of palliative care over the layer of standard clinical care, which is still not fully recognized by insurers and organizations. So, I think there’s also some systemic barriers that have to be overcome in integrating this truly.

Articles

Evidence-Based Oncology

Interviews with researchers and opinion leaders that took place during the 61st American Society of Hematology Annual Meeting and Exposition in Orlando, Florida, December 7-10, 2019.

AJMCtv Interviews: ASH19 Edition

At ASH, Data on Truxima Underscore the Biosimilar's Safety and Efficacy 

Celltrion and Teva's Biosimilar Rituximab, CT-P10 (Truxima), recently launched in the United States. The product is the first rituximab biosimilar to become available to patients in the United States,

 and during the 61st meeting of the American Society of Hematology (ASH) held from December 7-10, 2019, a pair of research teams presented data that highlight the biosimilar’s safety and efficacy in patients with lymphoma.

New phase 3 data show similar safety and efficacy between CT-P10, reference 

First, a team presented on updated phase 3 study results from a clinical trial of the biosimilar in 140 patients with newly diagnosed advanced-stage follicular lymphoma.

 Previously reported results from the same trial showed similarity between the biosimilar and the reference product, Rituxan, in terms of progression-free survival (PFS) and overall survival (OS) at a median follow-up of 22.6 months. In the study, 70 patients received biosimilar rituximab with cyclophosphamide, vincristine, and prednisone, and 70 patients received the reference with the same regimen, for 8 cycles. Of these patients, 62 in the biosimilar group and 60 in the

reference group entered the rituximab monotherapy maintenance period after induction therapy, and 46 and 38 patients, respectively, completed the maintenance

period of 2 years. After 2 years, patients were followed for tumor evaluation up to 3 years from the last patient’s first infusion.

For investigator-assessed PFS, time to progression (TTP), and OS, medians have not been reached in either group (median follow-up durations: 40 months in the CT-P10 group and 39 months in the reference group). There were no significant differences between the groups in terms of PFS (hazard ratio [HR], 1.33; 95% CI, 0.67-2.63; 4-year PFS for CT-P10, 60.9%; 95% CI, 46.5%-72.5%; 4-year PFS for reference, 54.7%; 95% CI, 36.1%-70.0%).

There were also no signifi cant diff erences in TTP (HR, 1.17; 95% CI, 0.58-2.37; 4-year TTP for CT-P10, 64.2%; 95% CI, 49.4%-75.7%; 4-year TTP for reference,

55.8%; 95% CI, 36.8%-71.1%). OS was comparable between the groups (4-year OS for CT-P10, 88.0%; 95% CI, 77.5%-93.8%; 4-year OS for reference, 93.3%; 95% CI, 83.2%-97.4%; P = .287).

In total, 30% of patients in each group experienced disease progression. Five patients in the biosimilar group and 2 patients in the reference group died during the study period. No new safety signals were identified, and similar numbers of patients in each group experienced at least 1 treatment-emergent adverse event.

Rapid infusion with CT-P10 is well tolerated 

Second, another group of researchers reported on a postauthorization safety study of the biosimilar that is currently underway in several European nations.

 The study concerns rapid infusion of the biosimilar, over a period of 90 minutes or less, during routine clinical practice.

In Europe, the recommended protocol for rituximab infusion is a slow initial infusion rate with a gradual upward titration, but rapid infusion is often used in second or subsequent infusions for patients who had no serious complications with a first infusion.

In the study, 112 patients with lymphoma who had between 1 and 4 prior infusions with CT-P10 were given subsequent rapid infusions over a 6-month observation. In total, 19 patients experienced 1 or more infusion-related reactions (IRRs). Of these patients, 9 had 1 IRR, 5 had 2 IRRs, and 5 had 3 or more IRRs.

The best responses to rituximab therapy during the observation period were complete response in 74% of patients, partial response in 21% of patients, stable disease in 3% of patients, and progressive disease in 2% of patients, said the investigators. 

1. Davio K. First rituximab biosimilar Truxima launches in the United States. The Center for Biosimilars® website. centerforbiosimi lars.com/news/first-rituximab-biosimilar-truxima-launches-in-the-united-states. Published November 7, 2019. Accessed December 11, 2019.

2. Buske C, Kwak LW, Jurczak W, et al. Long-term efficacy and safety results of CT-P10 and reference rituximab in patients with newly diagnosed advanced stage follicular lymphoma: phase III updated study results with median follow-up of 40 months. Presented at: 61st Annual Meeting and Exposition of the American Society of Hematology; December 7-10, 2019; Orlando, FL. Abstract 1528.

Data on Complement Inhibitors and Proposed Biosimilars Featured at ASH

3. Bishton M, Zinzani PL, Marshall S, et al. Rapid infusion with CT-P10 in patients with non-Hodgkin’s lymphoma or chronic lymphocytic leukemia: interim six month follow-up from a European non-interventional post-authorization study. Presented at: 61st Annual Meeting and Exposition of the American Society of Hematology; December 7-10, 2019; Orlando, FL. Abstract 4135.

Eculizumab, a C5 complement inhibitor, has changed the treatment landscape for several rare diseases, including paroxysmal nocturnal hemoglobinuria (PNH), myasthenia gravis, and atypical hemolytic uremic syndrome. However, the drug, sold by developer Alexion as Soliris, is among the most expensive biologic therapies in the world—carrying a cost of approximately $500,000 per patient per year

—and that cost has an impact on patient access. 

Multiple biosimilar developers are taking aim at eculizumab, however, and at the same time, Alexion is continuing to invest in a longer-acting successor to eculizumab as biosimilars draw closer. During the 61st meeting of the American Society of Hematology (ASH), investigators reported on eculizumab, a prospective biosimilar, and the longacting ravulizumab.

Investigators report on PK and ADAs for proposed biosimilar eculizumab, ABP 959 

Amgen is developing ABP 959, a proposed biosimilar to eculizumab, and the product has’previously been reported to have pharmacokinetic (PK) and pharmacodynamic equivalence with the reference Soliris.

During ASH, researchers reported on an assessment of the relationship between PK parameters and antidrug antibodies (ADAs) for the proposed biosimilar and the reference.

 Their data derive from a randomized, double-blind, single-dose, 3-arm, parallel-group study in healthy male volunteers.

 In the study, the 219 participants were randomized to receive 300 mg of either the biosimilar (n = 71), its US-licensed reference (n = 74), or its EU-licensed reference (n = 74), and serum samples for PK evaluation were collected over 57 days.

No neutralizing antibodies were detected during the study. At any time, the incidence of binding ADAs was 9.9% in the biosimilar group, 6.9% in the US reference group, and 9.5% in the EU reference group. At the end of the study, 1.9% of participants had binding ADAs, with 1.4% in the biosimilar group, 2.9% in the US reference group, and 1.4% in the EU reference group testing positive for these ADAs.

In those who had binding ADAs, PK was within the same range as it was in those without any ADAs detected, per the authors. Furthermore, the incidence of ADAs was similar between products and did not aff ect the overall PK similarity assessment.

Relatively few US patients with PNH start treatment with eculizumab Complement inhibition is becoming the standard of care in treating PNH, but given the fact that PNH is a rare disease, little is known about how patients are managed after diagnosis in real-world practice.

Using Truven US MarketScan commercial and Medicare data from 2015 to 2018, researchers sought to estimate the incidence and prevalence of PNH and to describe real-world treatment in patients who are newly diagnosed with the blood disease.

They found that the incidence rate over the study period was 5.7 per 1,000,000 person-years, or 257 new diagnoses. Over a mean follow-up time of 385.6 days (SD, 253.2), just 10.3% of patients started eculizumab (95% CI, 6.3%-14.1%), initiating the drug 60.5 days (SD, 55.9 days) after diagnosis. At 1 year, approximately one-third of patients had discontinued eculizumab or taken a break in treatment.

Future studies should explore factors related to initiating eculizumab, say the investigators, as well as those related to treatment persistence.

Successor to eculizumab proves effective, safe at week 52

Meanwhile, ravulizumab, Alexion’s longeracting C5 complement inhibitor that offers’less frequent administration than eculizumab, was also the subject of a presentation of new data. Researchers presented 1-year safety and efficacy data from a phase 3 study in patients with PNH who had received eculizumab and transitioned to ravulizumab.

Previously, treatment every 8 weeks with ravulizumab was shown to be noninferior to treatment every 2 weeks with eculizumab at 26 weeks. The new data, up to 52 weeks, derive from an extension of the open-label trial. In the extension, patients who had received ravulizumab continued maintenance therapy, and those who had received eculizumab switched to ravulizumab. In total, 191 of 192 patients in the study entered the extension, and 96 were in the ravulizumab-only group, whereas the

Patients in both groups showed a durable response for percent change in lactate dehydrogenase at 52’weeks; patients in the ravulizumab-only group had an 8.8% increase in lactate dehydrogenase from baseline (SD, 29%), whereas patients in the switch group had a 5.8% change (SD, 27%).’

During weeks 0 to 26, 88% of patients in the ravulizumab-only group avoided transfusion, versus 87% of patients in weeks 27 to 52. In the switch group, 83% avoided transfusion during both periods. During the extension period, 79% of patients in the ravulizumab-only group and 75% in the switch group had a treatment-emergent adverse event. Eight patients (8%) in the ravulizumab-only group and 5 (5%) in the switch group experienced serious adverse events, none of which led to discontinuation or death.

According to the researchers, ravulizumab continues to be well tolerated at week 52, with no new safety concerns arising in the extension, and the drug appears to have durable efficacy.

1. Elgin B, Bloomfield D, Chen C. When the patient is the gold mine. Bloomberg Businessweek website. www.bloomberg.com/news/features/2017-05-24/when-the-patient-is-a-gold-mine-the-trouble-withrare-disease-drugs. Published May 30, 2017. Accessed December 11, 2019.

2. Amgen’s eculizumab biosimilar ABP 959, shows PK, PD bioequivalence to Soliris. The Center for Biosimilars® website. www.centerforbiosimilars.com/conferences/eha-2019/amgens-eculizumab-biosimilar-abp-959-shows-pk-pd-bioequivalence-to-soliris-. Published June 18,

3. Hanes V, Pan J, Mytych DT, Chien D, Chow V. Relationship between pharmacokinetics and antidrug antibody status of ABP 959, a biosimilar candidate to eculizumab: results from a pharmacokinetic similarity study. Presented at: 61st Annual Meeting and Exposition of the American Society of Hematology; December 7-10, 2019; Orlando, FL. Abstract 3520. www.ash.confex.com/ash/2019/webprogram/Paper128621.html.Accessed December 10, 2019.

4. Jalbert JJ, Chaudhari U, Zhang H, Weyne J, Shammo JM. Epidemiology of PNH and real-world treatment patterns following an incident PNH diagnosis in the US. Presented at: 61st Annual Meeting and Exposition of the American Society of Hematology; December 7-10, 2019; Orlando, FL. Abstract 3407. www.ash.confex.com/ash/2019/webprogram/Paper125867.html. December 10, 2019.

5. Kulasekararaj A, Hill A, Langemeijer S, et al. One-year efficacy and safety from a phase 3 trial of ravulizumab in adult patients with paroxysmal nocturnal hemoglobinuria receiving prior eculizumab treatment. Presented at: 61st Annual Meeting and Exposition of the American Society of Hematology; December 7-10, 2019; Orlando, FL. Abstract 2231. www.ash.confex.com/ash/2019/webprogram/Paper128746.html. December 10, 2019.

Results for Truxima, recently launched in the United States, and complement inhibitors were presented at the 61st American Society of Hematology Annual Meeting and Exposition.

Biosimilars at ASH 2019: Data on Truxima and Competitors for Eculizumab 

Data presented at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition on the fi xed-dose combination of daunorubicin and cytarabine, known as CPX-351 and sold as Vyxeos by Jazz Pharmaceuticals, led to fewer inpatient days than patients treated with the conventional regimen for secondary acute myeloid leukemia (sAML).

The results were based on data from the Premier Healthcare Database and involved 195 patients treated with CPX-351 and 160 eligible for CPX-351 but treated with the 7+3 regimen, which consists of cytarabine administration for 7 days and short infusions of anthracycline for the fi rst 3 days. By contrast, CPX-351 is a liposome-encapsulated combination of daunorubicin and cytarabine at a synergistic 1:5 molar ratio.

The abstract presented by Kwanza Price, MPH, of Jazz Pharmaceuticals, gathered data from August 1, 2017, and February 28, 2019, capturing the first 19 months of claims data after the biotech received FDA approval for its fixed-dose therapy for 2 types of poor-prognosis acute myeloid leukemia (AML).

Patients captured in the retrospective observational study had a median age of 68 years for the CPX-351 group and a median age of 61 years for the 7+3 group. Male patients made up 62.6% of the CPX-351 group and 55% of the 7+3 group. White patients comprised 72.3% of the patients in the CPX-351 group and 75% of the patients in the 7+3 group. The median length of follow-up was 136 days for the CPX-351 group and 126 days for the 7+3 group.

The median inpatient length of stay per patient year (PPY) was shorter in the CPX-351 group compared with those in 7+3 group (nominal P = .068).

Although the median hospital costs PPY in the CPX-351 group were higher (nominal P < .001), the nondrug medical cost PPY was not higher (nominal P = .785).

Separate data presented at ASH showed that CPX-351 improved overall survival (OS) in patients with therapy-related AML (t-AML).3 CPX-351 also improved OS in patients who had a stem cell transplant compared with patients who underwent a transplant, treated with the traditional 7+3 regimen in the subgroup of patients with AML who had a history of myelodysplastic syndrome (MDS) or MDS/myeloproliferative neoplasm who achieved complete response or complete response with incomplete neutrophil or platelet recovery.

) asked Robert Iannone, MD, MSCE, executive vice president of research and development at Jazz Pharmaceuticals, to discuss the results presented at ASH:

The diff erent data sets presented at ASH showed that CPX-351 extends survival time relative to standard of care (7+3) while also reducing the amount of time patients spend in the hospital. What has been the response from physicians regarding these fi ndings?

: While we don’t have specifi c feedback to share, the ability to extend survival time— and potentially provide older patients with sAML a better chance for remission, which can help them prepare for transplant&mdash;is a positive, and an advancement over traditional chemotherapy. Combined with a possible reduction in the amount of time hospitalized, we are confi dent in the value that Vyxeos provides to physicians as well as to patients.

 Can you discuss the ability of CPX-351 to address areas of unmet need?

: Vyxeos is the fi rst and only chemotherapy treatment option for patients diagnosed with 2 types of secondary (sAML), t-AML and AML with myelodysplasia-related changes. Vyxeos provides these patients with a better chance for remission, which can help them prepare for transplant, representing an advancement over traditional chemotherapy. Vyxeos has also been shown to deliver signifi cant improvement in both OS and complete remission rates compared to the current standard of care, 7+3 (daunorubicin and cytarabine), based on robust phase 3 program data.

As the leukemia treatment landscape evolves, we understand the potential of combination therapy for this diffi cult-to-treat patient population. We are committed to exploring the full potential of Vyxeos as the key component in combination with other therapies to address currently unmet needs.

 What is the importance of these fi ndings to the ability of physicians to get patients to transplant?

: As mentioned, for older patients with sAML, Vyxeos provides a better chance for remission compared to traditional chemotherapy, which can help them prepare for transplant. It’s important for patients and oncologists to understand all treatment options. For appropriate older patients with sAML, intensive chemotherapy followed by hematopoietic stem cell transplant is a treatment option with curative intent.

 Can you describe your conversations with payers and what questions they have? Are you encountering barriers to prior approval or access?

: We can’t share any specifi cs of our conversations with payers. We are pleased that the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology for AML were updated in September 2019, granting Vyxeos category 1 for patients with t-AML or antecedent MDS/chronic myelomonocytic

leukemia¯ or AML with myelodysplasia-related changes who are 60 and older. Vyxeos is the only category 1 recommendation for these patients. We are pleased with the access Vyxeos has, and for the overwhelming majority of accounts across the country, we have not encountered barriers to prior approval or access.

 What are the next research questions on the horizon for CPX-351?

: We are very interested in the potential of combination therapy, and we’re committed to exploring the full potential of Vyxeos as the key component in combination with other therapies. Planned studies of Vyxeos in combination with other treatments—including venetoclax, gemtuzumab, and various targeted therapies&mdash;will explore the potential for these combination treatments to reach more patients.  

We’re also continuing to explore diff erent dosages, strengths, and schedules of Vyxeos with the goal of adjusting for patient ability to manage treatments, in particular for both fi t and unfi t patients, as well as standard- and high-risk AML in newly diagnosed patients.

MDS also remains an area of great interest to Jazz, and we’re working to test Vyxeos in this population.

Finally, we’re curious—what is the origin of the name Jazz Pharmaceuticals?

: In music, jazz is the art of harnessing individual talents through collaboration, improvisation, and constant evolution. It’s unique in its sound and composition, and the connections it creates are personal. In healthcare, it is much the same. We chose the name Jazz because it refl ects not only how we approach our business but also—and more importantly&mdash;how we approach our responsibility to change people’s lives. 

1. Price K, Cao Z, Lipkin C, Robinson S, Profant DA. A descriptive study on healthcare utilization costs in secondary acute myeloid leukemia patients treated with CPX-351 versus those treated with 7+3. Paper presented at: 61st American Society of Hematology Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL; Abstract 2213. http://ash.confex.com/ash/2019/webprogram/Paper127075.html. Accessed December 20, 2019.

2. FDA approves first treatment for certain types of poor-prognosis acute myeloid leukemia [press release]. Silver Spring, MD: FDA Newsroom; August 3, 2017.

3. www.fda.gov/news-events/press-announcements/fda-approves-firsttreatment-certain-types-poor-prognosis-acute-myeloid-leukemia. Accessed December 20, 2019.

4. Lancet JE, Rizzieri DA, Schiller GJ, et al. Outcomes in patients with therapy-related acute myeloid leukemia (t-AML) who achieved remission with CPX-351 versus 7+3: phase 3 exploratory analysis. Paper presented at: 61st American Society of Hematology Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL; Abstract 1313. ash.confex.com/ash/2019/webprogram/Paper124383.html. Accessed December 20, 2019.

5. Ryan DH, Newell LF, Ritchie EK, et al. Outcomes in patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) who achieved remission with CPX-351 versus 7+3: phase 3 exploratory analysis. Paper presented at: 61st American Society of Hematology Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL; Abstract 3842. http://ash.confex.com/ash/2019/webprogram/Paper124516. html. Accessed December 20, 2019.

The abstract presented by Kwanza Price, MPH, of Jazz Pharmaceuticals, gathered data from August 1, 2017, and February 28, 2019, capturing the first 19 months of claims data after the biotech received FDA approval for its fixed-dose therapy for 2 types of poor-prognosis acute myeloid leukemia.

ASH 2019 Interview: Data Show Fixed-Dose Daunorubicin Plus Cytarabine Leads to Fewer Inpatient Days for Patients With sAML

During oral abstract sessions at the 61st American Society of Hematology Annual Meeting & Exposition in Orlando, Florida, results from the MOST and CLL14 trials were presented on older patients being treated for essential thrombocythemia (ET)/myelofi brosis and chronic lymphocytic leukemia (CLL), respectively. Results showed signifi cant symptom burden, particularly from fatigue.

Both studies covered older patients, with a median age of 70 years (range, 19-93) for patients in MOST (80% were at least 60 years of age)

 and at least 71˜years for patients in CLL14.

 They both also used the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) to evaluate health-related quality of life (QOL) (functional ability), with MOST also using the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) for symptom burden and CLL14, the MD Anderson Symptom Inventory (MDASI). Patients were asked to report on symptom burden, functional status, and QOL at regular intervals throughout their treatment using provided questionnaires. These patient-reported outcomes (PROs) are meant to inform a greater understanding of how to improve QOL aff ected by treatment.

 patients on ET-directed therapy were observed for 36 months, and their data (also known as a score) were collected every 6 months. High scores indicated good results for functional status and QOL, but a signifi cant symptom burden. The mean (SD) TSS score (range, 0-100 overall; 0-10 per symptom) was 17.1 (15.6), with women faring worse than men (18.5 [15.8] vs 14.2 [14.9]). Fatigue had the highest individual mean symptom score (3.4 [2.7]), topping also the EORTC QLQ-C30 scale for severity, at 29.6 (25.8). The mean global health status/QOL score was 72.7 (21.9) (

). Men had overall higher functioning scores and less symptom

 432 patients received chlorambucil/obinutuzumab (Gazyva) (CIbG) or venetoclax/obinutuzumab (VenG). They were observed for a median 28.1 months, and their data (score) were collected every 3 months during follow-up. Again, high scores indicated good functional status and QOL, but a great symptom burden. EORTC physical and role function scores were a mean (SD) 75.9 (± 20.1) and 76.9 (± 19.4) in the CIbG and VenG arms (216 patients each), respectively, when treatment started, whereas QOL was 63.6 (± 21.0) and 60.3 (± 20.5), respectively. The VenG treatment group fared better more quickly, however, with meaningful improvement in QOL seen by cycle 3 of treatment compared with cycle 8 for the CIbG group (

 For MDASI, CLL (1.5 [± 1.2] and 1.6 [± 1.3]) and core cancer (1.5 [± 1.4] and 1.8 [± 1.7]) symptoms and symptom interference (2.1 [± 2.3] and (2.3 [± 2.3]) remained low and similar from baseline through follow-up for the VenG and CIbG groups, respectively (

).3 Overall, functional status and QOL did not worsen and symptom severity remained low among both groups, with dyspnea being the most severe symptom at baseline (24.8 [± 27.76]), compared with during treatment and follow-up.

Investigators from the MOST trial believe that “future analyses from this trial will continue to increase understanding of the symptom burden and its impact on QOL in patients with ET,” whereas CLL14 investigators note, “As elderly patients with CLL typically experience impairment of QOL, particularly when suff ering from various other conditions, such improvement should be considered a main therapeutic goal.”

1. Ritchie EK, Al-Janadi A, Colucci P, Kalafut P, Paranagama D, Mesa RA. Patient-reported outcomes (PRO) data from patients (pts) with essential thrombocythemia (ET) enrolled in the MOST study. Presented at: 61st American Society of Hematology Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL. Abstract 1665. ash.confex.com/ash/2019/webprogram/Paper124527.html. Accessed December 21, 2019.

2. A Study to Compare the Efficacy and Safety of Obinutuzumab + Venetoclax (GDC-0199) Versus Obinutuzumab + Chlorambucil in Participants With Chronic Lymphocytic Leukemia. clinicaltrials.gov/ct2/show/results/NCT02242942. Updated October 1, 2019. Accessed December 6, 2019.

3. Al-Sawaf O, Gentile B, Devine J, et al. Rapid improvement of patient-reported outcomes with venetoclax plus obinutuzumab in patients with

previously untreated CLL and coexisting conditions: a prospective analysis from the CLL14 trial. Presented at: 61st American Society of Hematology Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL. Abstract 4305. ash.confex.com/ash/2019/webprogram/Paper126542.html. Accessed December 21, 2019.

Patient-Reported Outcomes Are Considered During FDA Clinical Reviews

Disease symptoms, symptomatic adverse events, and physical function top the list of patient-reported outcomes (PROs) from cancer clinical trials of interest to the FDA during application reviews for both new products and new indications for existing medications.

 During the recent 61st American Society of Hematology Annual Meeting & Exposition in Orlando, Florida, for benign and malignant hematology indications, data were presented that show just how often the FDA consider s PROs during clinical review, when PROs are included in product labels, and what the PROs referenced.

Investigators from the FDA and the Center for Biologics Evaluation and Research (CBER) gathered PRO data for approvals between 2017 and 2018 from the Center for Drug Evaluation and Research in the Office of Hematology and Oncology Products and CBER, as well as determined the frequency with which those data were included on clinical study reports (CSRs)

, final FDA review, and drug labels. The FDA handed down 64 approvals during the study period (31 new molecular entity [NME]

The investigators determined that PRO data were included on 30% (3/10) of the CSRs for benign hematology NMEs and biologics license applications (BLAs) and 47% (7/15) of CSRs for malignancy applications. However, the FDA subsequently included that data in its clinical review for 9 submissions (3 benign; 6 malignant), and labels for Hemlibra (emicizumab; Chugai) and Rituxan Hycela (rituximab/hyaluronidase human; Genentech/Biogen) ultimately incorporated the data. Hemlibra

 treats hemophilia A, and Rituxan Hycela5®treats relapsed or refractory follicular lymphoma (FL), previously untreated FL, nonprogressing FL, previously untreated diffuse large B-cell lymphoma, and previously untreated and treated chronic lymphocytic leukemia (CLL). 

PRO data were also included on 38% (3/8) of the CSRs for supplemental benign hematology indications and 65% (13/20) for malignant indications. The FDA went on to include that data in its clinical review for 15 submissions (3, benign; 12, malignant), and labels for Feraheme (ferumoxytol; AMAG)

(ibrutinib; Pharmacyclics/Janssen Biotech) include the data. Feraheme treats iron deficiency anemia, and Imbruvica treats mantle cell lymphoma, CLL, CLL/small lymphocytic leukemia with 17p deletion, Waldenström’s macroglobulinemia, marginal zone lymphoma and chronic graft versus host disease.

Overall, more labels for benign indications (33% [1/3], NMEs and BLAs; 33% [1/3], supplemental) included PROs data than did those for malignant indications (16% [1/6] and 8% [1/12], respectively), and these data covered disease symptoms and physical function.

The FDA is currently developing guidelines for the use of PROs in cancer clinical trials.

1. Patient-centered initiatives at the FDA: a conversation with Vishal Bhatnagar, MD, Bellinda King-Kallimanis, PhD, Janice Kim, PharmD, and Paul G. Kluetz, MD. The ASCO Post. ascopost.com/issues/september-25-2019/patient-centered-initiativesat-the-fda/. Published September 25, 2019. Accessed December 12, 2019.

2. Navigating the four types of clinical study reports. MMS Holdings website. mmsholdings.com/navigating-the-four-types-of-clinical-studyreports/. Accessed December 12, 2019.

3. Chemicool Dictionary. Definition of molecular entity. chemicool.com/definition/molecular_entity.html. Accessed December 12, 2019.

4. Hemlibra (emicizumab-kxwh) injection, for subcutaneous use [package insert]. South San Francisco, CA: Genentech, Inc; 2018.

5. Rituxan Hycela (rituximab and hyaluronidase human) injection, for subcutaneous use [package insert]. South San Francisco, CA: Genetech,

6. Feraheme (ferumoxytol injection). [package insert]. Waltham, MA: AMAG Pharmaceuticals; 2018.

7. Imbruvia (ibrutinib) capsules, for oral use; Imbruvica (ibrutinib) tablets, for oral use [package insert]. Sunnyvale, CA, and Horsham, PA:

8. Kim J, Kanapuru B, Roydhouse JK, et al. 2017-2018 hematology drug approvals at the Food and Drug Administration (FDA): communication of patient-reported outcomes (PRO) information in FDA clinical reviews and prescribing information. Presented at: 61st American Society of Hematology Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL. Abstract 3450. ash.confex.com/ash/2019/webprogram/Paper125798.html. Accessed December 6, 2019.

Symptom burden, functional ability, and quality of life are necessary considerations when treating hematologic malignancies in older patients.

ASH 2019: Patient-Reported Outcomes, From MOST to FDA Clinical Reviews

Apixaban Is Linked to Large Reductions in Major Bleeding, Recurrent VTE in Active Cancer

Patients with cancer who took apixaban to prevent blood clots had a 37% reduction in major bleeding (MB) and a 39% reduction in recurrent venous thromboembolism (VTE) compared with those taking low-molecular weight heparin (LMWH), according to data presented on December 7, 2019, at the 61st American Society of Hematology Annual Meeting & Exposition in Orlando, Florida. Apixaban also had large reductions in VTE (32%) relative to warfarin.

A subgroup analysis presented alongside the main study found that apixaban’s benefi ts relative to LMWH held up across different types of cancer regardless of the risk level they present for VTE.

 Apixaban is sold as Eliquis by Bristol-Myers Squibb/Pfizer. Patients with active cancer—for this study, defined as cancer diagnosis or treatment in the 6 months before or 30 days after a VTE diagnosis&mdash;have a 4 to 7 times greater risk of developing VTE.

To gain more real-world evidence on the eff ectiveness and safety of LMWH compared with vitamin K antagonists, which emerged in the last decade as a treatment of VTE, and non-VKA anticoagulants, a team of researchers led by Alexander T. Cohen, MBBS, MSc, MD, of King’s College, London, evaluated the effi cacy of apixaban, LMWH, and warfarin among patients with active cancer. 

The investigators examined 3 groups of patients who started treatment within 30 days of their first VTE: 3393 apixaban users, 6108 LMWH users, and 4585 warfarin users. The mean ages were 65, 64, and 64 years, respectively. To evaluate rates of MB, clinically relevant non-MB (CRNMB), and recurrent VTE, the patients were followed to the earliest of 1 of 6 time points: health plan disenrollment, death, index therapy discontinuation, switch to another anticoagulant, study end, or a maximum of 6 months.

• Apixaban had lower risks of MB, CRNMB, and recurrent VTE compared with LMWH, with a hazard ratio (HR) of 0.63 (95% CI, 0.47-0.86; P = .003) for MB, an HR of 0.81 (95% CI, 0.70-0.94; P = .006) for CRNMB, and an HR of 0.61 for recurrent VTE (95% CI, 0.47-0.81; P = .001).

• Apixaban had lower rates of recurrent VTE and modest reductions of MB and CRNMB compared with warfarin, with an HR of 0.68 (95% CI, 0.52-0.90; P = .007) for recurrent VTE, an HR of 0.73 (95% CI, 0.53-1.0; P = 0.51) for MB, and an HR of 0.89 (95% CI, 0.77-1.04; P = 0.145) for CRNM. 

“Real-world evidence analyses such as this have the potential to provide additional insights into complex patient populations such as those with VTE and active cancer,” Cohen said in a statement.

“Results from these analyses are a welcomed addition to the growing body of data around recurrent VTE in patients with active cancer.”

In the second presentation, results from the subgroup analysis examined how apixaban aff ected recurrent VTE, MB, and CRNMB risk across diff erent cancer types relative to warfarin and LMWN.  Hematologic cancer, as well as those of the brain, pancreas, stomach, liver, lungs, and kidneys, are associated with a higher risk of VTE. Researchers used the Khorana risk score based on cancer type, blood counts, and body mass index to evaluate risk level and assess the safety of each therapy based on cancer type. Patients were categorized as having a very high risk of VTE, high risk of VTE, or other.

Results from the same real-world data set as the fi rst abstract showed that those taking apixaban had a lower risk of recurrent VTE compared with warfarin and a lower risk of MB, CRNMB, and recurrent VTE compared with LMWH, consistent with the overall results. Researchers called for more studies to evaluate the role of anticoagulants in high-risk subgroups of patients with cancer who have VTE.

Besides the risk of VTE, real-world evidence can be evaluated for other factors. Asked by 

™ if the patient data could be evaluated to see whether those with comorbidities had diff erent responses, Danny Wiederker, HEOR team lead at Pfi zer, said in an email, “Comorbidities are always an important consideration in real-world evidence, given some may be important confounders that impact both the treatment decision and the outcomes of interest. That’s why the Pfizer/BMS Alliance leverages the best research practices recommended by organizations like the International Society of Pharmacoeconomics and Outcomes Research that look to adjust for both comorbidities and patient factors, like age, gender, etc, that may impact outcomes.” 

He said the study being presented is the inverse probability of treatment weighting to adjust for confounding while including the broadest possible patient population.

“Our approach generally is to start with the broad population and then drill down into subgroups as we are also highly interested in better understanding in which patient populations there is even more unmet need and more opportunity to improve outcomes,” Wiederker said. “We have conducted the first subgroup analysis presented as the second oral presentation stratifying based on the risk of recurrent VTE level, but we also have interest in other subgroups and are exploring opportunities for additional analyses.”

1. Cohen AT, Keshishian A, Lee T, et al. Safety and effectiveness of apixaban, LMWH, and warfarin among venous thromboembolism patients with active cancer: a retrospective analysis using four US claims databases. Presented at: 61st American Society of Hematology Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL. Abstract 326. ash.confex.com/ash/2019/webprogram/Paper121769.html. Accessed December 7, 2019.

2. Cohen AT, Keshishian A, Lee T, et al. Safety and effectiveness of apixaban, LMWH and warfarin among venous thromboembolism (VTE) patients with active cancer: a subgroup analysis of VOTE risk scale. Presented at: 61 American Society of Hematology Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL. Abstract 327. ash.confex.com/ash/2019/webprogram/Paper126931.html. Accessed December 7, 2019.

3. Findings released from real-world data analysis of Eliquis (apixaban) for the treatment of venous thromboembolism in patients with active cancer [press release]. Princeton, NJ, and New York, NY: Businesswire. businesswire.com/news/home/20191207005040/en/Findings-Released-Real-World-Data-Analysis-Eliquis-apixaban. Accessed December 7, 2019.

Real-World Results Show Medicare Costs Drop After Completion of CAR T-Cell Therapy

Most Medicare patients treated with chimeric antigen receptor (CAR) T-cell therapies in the first year after FDA approval for diff use large B-cell lymphoma fared well after the procedure, according to an Avalere Health study presented at the 61stŸAmerican Society of Hematology Annual Meeting and Exposition in Orlando, Florida.

More than half of the patients treated with this expensive revolutionary therapy had comorbidities common in seniors, such as heart disease or renal problems, that might have kept them out of clinical trials. But 6 months after treatment, hospital stays dropped 17% from pretreatment levels. And healthcare costs 6 months after CAR T-cell therapy, based on Medicare Part A and B, were 39% lower than they were in the 6 months before treatment, said lead study author Karl M. Kilgore, PhD, who shared results from 207 patients in a press briefi ng on December 7, 2019. The study is the first claims analysis from Medicare patients who received CAR T-cell therapy in the year after October 1, 2017.

 The FDA approved Novartis’ tisagenlecleucel (Kymriah) in August, followed by Gilead’s axicabtagene ciloleucel (Yescarta), in October 2017. Both are approved to treat adults with relapsed or refractory large B-cell lymphoma.

Medicare patients in the Avalere study were more than a decade older than the median age of patients in clinical trials, yet many had good outcomes. “Our findings off er evidence that older patients with multiple comorbidities can be treated successfully with CAR T,” he said in a statement.

 “While we don’t know the long-term outcomes yet, nearly three-quarters of the patients were still alive 6 months posttreatment.”

Kilgore said this is the fi rst analysis to use real-world evidence—in this case, Medicare claims&mdash;to examine how CAR T-cell therapy works in older patients with other health issues. Although the Avalere study found a signifi cant decline in both healthcare utilization and cost, Kilgore was clear that this “is not a cost-effectiveness study,” meaning it was not designed to evaluate the healthcare savings seen after treatment against the cost and benefits of treatment itself. CAR T-cell therapy in this indication costs $373,000 just for the specially engineered therapy manufactured from a patient’s own cells. Administration costs, including the cost of treating adverse events, can easily drive the total price tag closer to $1 million.

Medicare and academic centers that off er CAR T-cell therapy have battled over reimbursement rates for more than a year, and while payment is set to rise in 2020, a commentary in the 

 in November estimated that centers lose $300,000 on every Medicare patient they treat.

• The median age of the Medicare patients was 71, compared with 56 to 58 years of age in clinical trials, and 51% of individuals in the Medicare group had 1 or more

• Results after 177 patients showed the drop in per-patient per-month healthcare utilization costs in Medicare Part A and B fell from $9749 in the period 6 months before CAR T-cell therapy to $7121 in the 6 months after therapy. Kilgore said in an interview with 

™ that Part D data had not been released in time for the American Society of Hematology meeting and would be analyzed separately.

• Six months after treatment, emergency department visits dropped by 45%, and the number of patients visiting the emergency department dropped by one-third.

• The study shed light on the healthcare needs of Medicare patients receiving CAR T-cell therapy—the average hospital stay for the procedure is 17 days. Less than half needed time in the intensive care unit; those that did stayed 13 days.

Kilgore noted that reimbursement methods to hospitals performing CAR T-cell treatment vary, with some subject to the acute inpatient prospective payment system rule, while others are exempt.

 The Avalere study found that the Centers for Medicare & Medicaid Services, on average, is reimbursing under the inpatient prospective payment system about $422,000, compared with $467,000 in the outpatient setting.

Joseph Alvarnas, MD, an oncologist/hematologist who serves as vice president of government affairs and senior medical director for employer strategy for City of Hope in Duarte, California, and is editor-in-chief of 

™, said that while the Avalere analysis is not a cost-eff ectiveness study or a comparative eff ectiveness model, “These data add to other data sets that continue to validate the idea that there is a real value proposition for these therapeutics, that provides a path toward developing an economically sustainable model for treating this population of patients.”

The authors acknowledge that the Medicare patient sample remains small and that it may not represent a broader patient population. Kilgore has received research funding from Kite Pharma, which developed the CAR T-cell product that Gilead acquired and launched Avalere’s results were part of a set of abstracts that highlighted results involving disparities in care. Other results include:

• A study of 1040 patients with acute myeloid leukemia (AML), presented by Abby Statler, PhD, MPH, of Cleveland Clinic, found that issues with renal function appear to be a barrier to enrollment in clinical trials for African Americans. However, there is no association between clinically insignificant renal lab values and response to treatment or overall survival (OS), so the study recommends adjusting trial eligibility criteria to reduce racial disparities in enrollment.

• Lena E. Winestone, MD, MSHP, of the University of California, San Francisco, presented data that show children with AML from middle- and high-income areas

experience a 25% lower mortality risk compared with those from low-income areas (OS, crude hazard ratio [HR], 0.74; 95% CI, 0.62-0.89; adjusted HR, 0.79; 95% CI, 0.63-0.99). Clinical trial data were matched with zip-code data as a proxy for income, and the authors of the study concluded that “zip-code—based low socioeconomic status is an independent risk factor for mortality in pediatric AML.”

• Anita D’Souza, MD, MS, of the Medical College of Wisconsin at Milwaukee, presented a large study of autologous hematopoietic cell transplantation in older adults with multiple myeloma (at least 70 years of age) and found that these older patients can safely undergo the transplant procedure with the same benefi ts that are seen in younger patients. Adjusted results show that compared with patients aged 60 to 69 years, those 70 years of age or older had similar nonrelapse mortality, with an HR of 1.3 (95% CI, 11.7; P = .06); progression-free survival; HR, 1.06 (95% CI 11.2, P = .2); and OS, with an HR of 1.2 (95% CI, 11.4; P = .02).

1. Kilgore K, Mohammadi I, Schroeder A, et al. Medicare patients receiving chimeric antigen receptor T cell therapy for non-Hodgkin lymphoma: a first real-world look at patient characteristics, healthcare utilization and costs. Presented at: 61st American Society of Hematology Annual Meeting and Exposition; December 7-10,

2019; Orlando, FL. Abstract 793. ash.confex.com/ash/2019/webprogram/Paper124364.html. Accessed December 7, 2019.

2. Rosenberg J. FDA approves CAR T-cell treatment Kymriah for adult B cell lymphoma. The American Journal of Managed Care® website. ajmc.com/newsroom/fdaapprovescartcelltreatmentkymriahforadultbcelllymphoma. Published May 2, 2018. Accessed December 10, 2019.

3. Studies offer mix of hope and challenges in addressing cancer care disparities [press release]. Orlando, FL: American Society of Hematology; December 7, 2019. apps.hematology.org/presskit/18.aspx. Accessed December 7, 2019.

4. Manz CR, Porter DL, Bekelman JE, et al. Innovation and access at the mercy of payment policy: the future of chimeric antigen receptor therapies [published November 1, 2019]. J Clin Oncol. doi:10.1200/JCO.19.01691.

5. Center for Medicare and Medicaid Services. Acute inpatient PPS. cms.gov/Medicare/MedicareFeeforServicePayment/AcuteInpatientPPS/

index. Updated November 15, 2019. Accessed December 7, 2019.

6. Statler A, Hobbs BP, Radivoyevitch T, et al. Are racial disparities in acute myeloid leukemia clinical trial enrollment associated with comorbidities and/or organ dysfunction? Presented at: 61stƒAmerican Society of Hematology Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL. Abstract  381. ash.confex.com/ash/2019/webprogram/Paper129096.html. Accessed December 7, 2019.

7. Whitestone LE, Getz KD, Bona KO, et al. Areabased socioeconomic disparities in survival of children with newly diagnosed acute myeloid leukemia: a report from the Children’s Oncology Group. Presented at: 61stƒAmerican Society of Hematology Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL. Abstract 703. ash.confex.com/ash/2019/webprogram/Paper130978.html. Accessed December 7, 2019.

8. Munshi PN, Hari P, Vesole DH, et al. Breaking the glass ceiling of age in transplant in multiple myeloma. Presented at: 61st American Society of Hematology Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL. Abstract 782. ash.confex.com/ash/2019/webprogram/Paper124804.html. Accessed December 7, 2019.

Reviews of apixaban in active cancer, Medicare costs after CAR T-cell therapy, and the need for financial assistance for novel therapies.

January 2020

AJMCtv Interviews: ASH19 Edition

Biosimilars at ASH 2019: Data on Truxima and Competitors for Eculizumab

ASH 2019 Interview: Data Show Fixed-Dose Daunorubicin Plus Cytarabine Leads to Fewer Inpatient Days for Patients With sAML

ASH 2019: Patient-Reported Outcomes, From MOST to FDA Clinical Reviews

ASH 2019: Real-World Evidence and Cost of Care

ASH 2019 Clinical Findings: CAPTIVATE, CANDOR, Blinatumomab, and More

CAR T-Cell Therapy and Beyond: UCART 19 and Anti-BCMA Therapy

CAR T-Cell Therapy and Beyond: Off-the-Shelf Therapies Among Innovations at ASH 2019