Real-World Evidence With Axicabtagene Ciloleucel CAR T-Cell Treatment Similar to ZUMA-1 Trial Findings

A multicenter retrospective study that evaluated the efficacy and safety of chimeric antigen receptor (CAR) T-cell treatment, axicabtagene ciloleucel (axi-cel; Yescarta), in a real-world setting produced a similar response as well as toxicity compared with the ZUMA-1 clinical trial results. Predictors of response included low day 0 C-reactive protein (CRP) and high absolute lymphocyte count at leukapheresis. The results were presented December 1, 2018, during the 60th American Society of Hematology (ASH) Annual Meeting & Exposition, held in San Diego, California.

The FDA approved axi-cel in October 2017,

 and long-term results for the treatment were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in June 2018.

 The results presented at ASCO showed the objective response rate (ORR) was 82% at 8.7 months, which had been maintained by the long-term 15.4-months follow-up time. The complete response (CR) rate was 58% at the long-term follow-up.

Caron A. Jacobson, MD, instructor in medicine, Department of Medical Oncology, Dana-Farber Cancer Institute, and first author of the study presented at ASH, said that in a real-world setting, eligibility criteria and patient management factors may be very distinct from a clinical trial setting. Therefore, bridging therapy may be needed between leukapheresis and treatment with the CAR T product.

Thus, the study examined patient and disease characteristics and biomarkers of response or toxicity following axi-cel treatment in a real-world setting. In this case, the settings were 6 US academic medical centers that used commercial axi-cel.

Among the 104 patients with lymphoma who were part of this retrospective study (median age was 63.8 years; range, 21-80), 94 (90%) had an European Cooperative Oncology Group (ECOG) performance status of 0-1 and 48 (46%) had a prelymphodepletion International Prognostic Index (IPI) score of ≥3. Twenty-eight (27%) patients had a prior autologous transplant and 3 (3%) had received a prior allogenic stem cell transplant. Forty-two patients (40%) each had bulky disease (tumor bulk >5 cm) and received bridging therapy following leukapheresis.

At a median follow-up of 5.6 months, 13 patients had their T cells collected but they did not receive CAR T-cell infusion: 6 patients had progressive disease, 2 patients had infections, 3 patients had technical issues with cell production, 1 patient had a CR to bridging therapy, and 1 patient had another malignancy diagnosed.

When evaluated in 95 patients, an overall response (OR) was observed in 67 (62%) patients. A CR was observed in 42 (44%) patients and a partial response (PR) in 25 (26%). Among 51 patients with a 6-month follow-up, an OR was observed in 22 (43%).

Half of the patients who had an initial PR and who were not being followed went on to have a CR, Jacobson said. The median duration of response was 4.9 months.

According to Jacobson, univariate analysis showed that ECOG performance status (

 = .029), and prior ibrutinib (Imbruvica) treatment (

 = .002) had a significant association with lack of response to treatment with axi-cel.

A majority (96%) of the treated patients experienced cytokine-release syndrome (CRS), a flare-up that is characterized by low/high fever and low blood pressure and can sometimes lead to capillary leak syndrome, according to Stephen J. Schuster, MD, of the Perelman School of Medicine.

In 17 (16%) patients, CRS was grade 3 or higher; 2 patients (2%) died. A median time to onset was 1 day (range, 0-14), symptoms associated with the flare-up lasted a median of 6 days (range, 1-27). Fifty-eight (55.7%) patients experienced neurotoxicity following treatment with axi-cel, 29 (50%) of whom had grade 3 or higher neurotoxicity. There was 1 fatality associated with this toxic effect. Neurotoxic effects had a median onset time of 5 days (range, 0-34) and lasted for a median of 8 days (range, 1-52 days). Patients received tocilizumab (Actemra; n = 70) and steroids (n = 66) to counter the toxicity, and 30% required a stay in an intensive care unit. Six patients died following disease progression, and 5 died from toxicity. Univariate analysis that the researchers conducted for toxicity, mainly grade 3 or higher CRS or neurotoxicity, found no association with performance status, tumor bulk, IPI, prior treatment, bridging therapy, or eligibility for ZUMA-1.

Cytogenetic and immunohistochemistry staining found that 3 patients with programmed death ligand -1 postive (PD-L1) tumors were refractory to CAR T-cell therapy. Based on the staining results, a positive response could be associated with increased expression of PD-1, 41BB, ICOS, and Ki67, as well as CC3 indicating apoptosis, when CAR T-cell levels peaked by day 7. Subsequently, CAR T cells fell by day 14.

Jacobson said that the deviation from the observations in the ZUMA-1 trial may be due to the inclusion of sicker patients with a poorer performance status and possible different histologies in this patient population. Although rates of CRS and neurotoxicity were similar to ZUMA-1, toxicity was not associated with tumor bulk or response, but with higher peak inflammatory markers and absolute lymphocyte count, indicative of peak CAR T-cell levels.

“Unique combination approaches are necessary for specific patients/tumors,” she noted, adding that their trial results support the use of axi-cel outside of strict clinical trial criteria, although the outcomes may be slightly inferior.

Jacobson CA, Hunter B, Armand P, et al. Axicabtagene ciloleucel in the real world: outcomes and predictors of response, resistance and toxicity. In: Proceedings from the American Society of Hematology; December 1-3, 2018; San Diego, CA. Abstract 92. ash.confex.com/ ash/2018/webprogram/Paper117199.html.

FDA approves CAR T-cell therapy to treat adults with certain types of large B-cell lymphoma [press release]. Silver Spring, MD: FDA; October 17, 2018. www.fda.gov/newsevents/newsroom/pressannouncements/ucm581216.htm. Accessed December 1, 2018.

Dangi-Garimella S. ZUMA-1: response to axi-cel at 3 months prognostic for remission in B-cell lymphoma. 

Dr Stephen Schuster: unique CAR T toxicities require provider education. 

 website. ajmc.com/conferences/ash-2017/dr-stephen-schus- ter-unique-car-t-toxicities-require-provider-education. Published April 17, 2018. Accessed December 1, 2018.

Articles

Evidence-Based Oncology

Updates from the Annual ASH meeting, December 2018.

Clinical: CAR T-Cell Therapy

Ibrutinib Alone Better Than Chemoimmunotherapy as Frontline in Older Patients With CLL

According to the results of Alliance A041202, an international multicenter phase 3 trial, ibrutinib (Imbruvica) produces superior progression-free survival (PFS) compared with standard chemoimmunotherapy (CIT) in older patients with chronic lymphocytic leukemia (CLL), and adding rituximab (Rituxan) does not improve the ibrutinib response.

 The results were presented as part of the plenary session on December 2, 2018, at the 60th American Society of Hematology (ASH) Annual Meeting & Exposition in San Diego, California.

Accounting for about 25% to 30% of US leukemia cases, the American Cancer Society reports that nearly 21,000 new cases of CLL were diagnosed last year and the disease was responsible for about 4500 deaths.

CIT has been the gold standard for patients, with bendamustine plus rituximab (BR) being a standard, more aggressive CIT regimen for patients age 65 or older. The Bruton tyrosine kinase inhibitor ibrutinib was approved by the FDA in 2016 for CLL,

 but it’s only been compared with chlorambucil in this patient population, not with aggressive CIT. Also, the impact of adding rituximab to the ibrutinib treatment has not been evaluated, explained Jennifer A. Woyach, MD, associate professor, The Ohio State University College of Medicine, Columbus.

“Older patients are underrepresented in CLL clinical trials, unless the trial has been specifically designed for them,” Woyach said.

Data from the RESONATE-2 trial presented at the 2017 ASH annual meeting compared treatment-nai&#776;ve patients receiving ibrutinib as a single agent or chemoimmunotherapy regimens with patients with CLL who were receiving various combination treatments. Based on their results, the authors recommended that single-agent ibrutinib could be used in place of the combination chemotherapy regimens.

The Alliance A041202 trial has 3 treatment arms—BR (arm 1), ibrutinib alone (arm 2), and ibrutinib plus rituximab (arm 3)&mdash;which are designed to determine whether ibrutinib-containing regimens lead to superior PFS compared with CIT in treatment-nai&#776;ve older patients.

 PFS was defined as the time from randomization to first detection of disease progression or death. Additionally, this study sought to determine if adding rituximab to ibrutinib would prolong PFS over ibrutinib alone, Woyach said. The trial design allowed patients on arm 1 who progressed to cross over to arm 2. Data for the presentation at the ASH meeting were locked on October 4, 2018, Woyach added.

For trial inclusion, patients had to be 65 years or older with previously untreated, symptomatic CLL; creatinine clearance had to be at least 40 mL/min; bilirubin had to be ≤1.5 the upper limit of normal; and patients should have had no significant life-limiting intercurrent illness or need for warfarin treatment. Of the 644 patients who were screened, 547 were randomized 1:1:1 to the 3 arms. Thirty patients in the BR arm crossed over to the ibrutinib-alone arm following analysis.

The median age of trial enrollees was 71 years (range, 65-89) and a majority (67%) were men. High-risk Rai stage (stage III/IV) was detected in 54% of patients, unmethylated Zap-70 in 53%, del(17p) or del(11q) by local fluorescence in situ hybridization analysis in 25%, and complex karyotype in 29%.

PFS was higher in the ibrutinib-alone cohort compared with the ibrutinib-plus-rituximab cohort, Woyach said. In the eligible patient population, at a median follow-up of 24 months, 74%

of patients in arm 1 were alive and progression-free (95% CI, 66%-80%) compared with 87% in arm 2 (95% CI, 81%-92%) and 88% in arm 3 (95% CI, 81%-92%).

No significant differences in PFS were observed in the 2 ibrutinib arms among patients with a complex karyotype, she said. Two-year PFS estimates were 59%, 39%, and 87% in arms 1, 2, and 3, respectively. Overall response rates in the intent-to-treat population were 81%, 93%, and 94%, respectively, and the complete response rates were 26%, 7%, and 12%.

“We did not observe any significant differences in overall survival [OS] among the arms, which might be due to the crossover or the short follow-up time,” Woyach said. She reported that median OS had not been reached for any arm, and OS estimates were 95%, 90%, and 94% for arms 1, 2, and 3, respectively, at a 38-months follow-up.

Adverse events (AEs) were observed at a significantly high rate in this trial. Hematologic AEs were observed in 61%, 41%, and 38% of patients in arms 1, 2, and 3, respectively. Nonhematologic AEs were observed in 63%, 74%, and 74%.

“Hematologic AEs were prevalent in the BR arm while nonhematologic AEs were more common in the ibrutinib arms,” Woyach said. “Unexplained or unwitnessed death over the entire observation period was seen in 2 [1.1%], 7 [3.9%], and 13 [7%] patients in arms 1, 2, and 3 respectively.”

Concluding her presentation, Woyach said that the findings from their trial justify using ibrutinib as a standard-of-care treatment for patients 65 and older and that combining it with rituximab does not improve PFS outcomes. “Clinical trials of this patient population are still of high clinical interest, and the coop- erative group setting remains a reasonable avenue to complete these large studies,” she added.

Woyach JA, Ruppert AS, Heerema NA, et al. Ibrutinib alone or in combination with rituximab produces superior progression free survival (PFS) compared with bendamustine plus ritux- imab in untreated older patients with chronic lymphocytic leukemia (CLL): results of Alliance North American Intergroup Study A041202. In: Proceedings from the American Society of Hematology; December 1-3, 2018; San Diego, CA. Abstract 6. ash.confex.com/ash/2018/ webprogram/Paper116653.html.

American Cancer Society. Key statistics for chronic lymphocytic leukemia. ACS website. cancer.org/cancer/chronic-lymphocytic-leukemia/about/key-statistics.html. Updated May 10, 2018. Accessed December 2, 2018.

FDA approves Imbruvica (ibrutinib) for the first-line treatment of chronic lymphocytic leukemia [press release]. North Chicago, IL: PR Newswire; March 4, 2016. drugs.com/ newdrugs/fda-approves-imbruvica-ibrutinib-first-line-chronic-lymphocytic-leukemia-4353. html. Accessed December 3, 2018.

Dangi-Garimella S. Single-agent ibrutinib promising in MCL and CLL, improves patient well-being. 

website. ajmc.com/journals/evidence-based-oncology/2018/january-2018/single-agent-ibrutinib-promising-in-mcl-and- cll-improves-patient-well-being. Accessed December 2, 2018.

Rituximab and Bendamustine Hydrochloride, Rituximab and Ibrutinib, or Ibrutinib Alone in Treating Older Patients With Previously Untreated Chronic Lymphocytic Leukemia. clinical- trials.gov/ct2/show/NCT01886872. Updated November 2, 2018. Accessed December 2, 2018.

iLLUMINATE: Superior PFS With Ibrutinib—Obinutuzumab Even in High-Risk, Untreated CLL/SLL

Ibrutinib combined with obinutuzumab had better progression-free survival (PFS) at 30 months than the standard chemo- immunotherapy regimen, chlorambucil plus obinutuzumab, regardless of high-risk genomic features in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) who had never been treated.

Carol Moreno, MD, presented results from iLLUMINATE December 3, 2018, at the 60th American Society of Hematology Annual Meeting & Exposition, held in San Diego, California.

Ibrutinib is a first-in-class, once-daily inhibitor of Bruton tyrosine kinase and was approved in 2016

 in the United States as a single-agent, chemotherapy-free regimen for patients with CLL. The iLLUMINATE trial is a phase 3, open-label, multicenter trial that was designed to test the efficacy of ibrutinib with obinutuzumab versus chlorambucil with obinutuzumab in treatment-nai&#776;ve patients with CLL and SLL.

 Eligibility criteria included treatment-nai&#776;ve CLL/SLL and ≥65 years or <65 years with coexisting conditions (Cumulative Illness Rating Scale score >6, creatinine clearance <70 mL/min, and/or del(17p) or TP53 mutation).

One set of patients received 6 cycles of 420-mg ibrutinib once daily, combined with obinutuzumab 1000 mg on days 1/ 2, 8, and 15 of cycle 1, and day 1 of subsequent 28-day cycles. The other set of patients was treated with 6 cycles of chlorambucil, which was 0.5 mg/kg on days 1 and 15 of each 28-day cycle, combined with obinutuzumab, in the same dose and frequency as above. PFS was the primary endpoint, and secondary endpoints included PFS in a high-risk population—del(17p)/TP53 mutation, del(11q), and/or unmutated IGHV&mdash;rate of undetectable minimal residual disease, overall response rate (ORR), overall survival (OS), and safety. The trial allowed crossover of patients with confirmed progression in the chlorambucil—obinutuzumab arm to single-agent ibrutinib.

The trial enrolled 229 patients, 113 of whom were randomized to the ibrutinib—obinutuzumab arm and 116 to the chlorambucil– obinutuzumab arm. Median age was 71 years (range, 40-87) and 65% of patients had the above listed high-risk genomic features.

With a median follow-up of 31.3 months, patients who were treated with ibrutinib—obinutuzumab had a significantly better PFS compared with the comparator arm (median not reached [NR] vs 19.0 months; HR, 0.231; 95% CI, 0.145-0.367; 

 <.0001). At 30 months, the PFS rates were 79% with ibrutinib—obinutuzumab and 31% with chlorambucil–obinutuzumab. These were PFS results as assessed by an independent review committee (IRC), the authors reported.

Investigator (INV)-assessed PFS showed a similar trend for ibrutinib—obinutuzumab versus chlorambucil–obinutuzumab (median PFS NR vs 21.9 months; HR, 0.260; 95% CI, 0.163-0.415; 

 <.0001). Further, the improvements in PFS seen among patients receiving ibrutinib—obinutuzumab were independent of their genomic status compared with the comparator arm (median NR vs 14.7 months; HR, 0.154; 95% CI, 0.087- 0.270; 

Both IRC- and INV-assessed ORR were better for the ibrutinib-obinutuzumab arm. IRC-assessed ORR was 88% with ibrutinib and obinutuzumab versus 73% with the comparator, and INV-assessed ORRs were 91% and 81%, respectively. Similar trends were observed with the IRC-assessed complete response (CR) rate, which was higher with ibrutinib and obinutuzumab (19% vs 8%). INV-assessed CR rates were 41% and 16%, respectively.

The authors report similar 30-month OS rates: 86% in the ibrutinib—obinutuzumab arm and 85% in the chlorambucil and obinutuzumab arm, with 40% of patients randomized to chlorambucil–obinutuzumab receiving single-agent ibrutinib as second-line therapy. Over a median follow-up of 31.3 months, 4% of patients in the ibrutinib–obinutuzumab arm and 44% in the chlorambucil–obinutuzumab arm initiated subsequent therapy.

The most frequent (≥3%) serious adverse events (AEs) among patients in the ibrutinib—obinutuzumab arm were pneumonia (5%), atrial fibrillation (4%), febrile neutropenia (4%), and pyrexia (4%). The more common serious AEs in the chlorambucil–obinutuzumab were infusion-related reactions (IRRs; 7%), febrile neutropenia (6%), pneumonia (4%), tumor lysis syndrome (4%), and pyrexia (3%). Although no patients discontinued obinutuzumab due to IRRs in the ibrutinib and obinutuzumab arm, 7 patients in the comparator stopped obinutuzumab.

AEs leading to discontinuation of ibrutinib and chlorambucil occurred in 18 (16%) and 11 patients (9%), respectively, and AEs leading to discontinuation of obinutuzumab occurred in 10 patients (9%) in the ibrutinib—obinutuzumab arm and 15 (13%) in the chlorambucil–obinutuzumab arm.

At about the 3-year follow-up mark, 70% of patients in the ibrutinib—obinutuzumab arm were on single-agent ibrutinib.

Based on their findings, the authors concluded that the ibrutinib—obinutuzumab combination therapy was tolerable among treatment-nai&#776;ve patients with CLL/SLL, with no new safety signals identified, and that it represents an effective chemotherapy-free treatment option for first-line CLL/SLL, including among the high-risk population.

Moreno C, Greil R, Demirkan F, et al. Ibrutinib + obinutuzumab versus chlorambucil + obinutuzumab as first-line treatment in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL): results from phase 3 iLLUMINATE. In: Proceedings from the American Society of Hematology; December 1-4, 2018; San Diego, CA. Abstract 691. ash. confex.com/ash/2018/webprogram/Paper111370.html.

FDA approves Imbruvica (ibrutinib) for the first-line treatment of chronic lymphocytic leukemia [press release]. North Chicago, IL: PR Newswire; March 4, 2016. drugs.com/newdrugs/fda-approves-imbruvica-ibrutinib-first-line-chronic-lymphocytic-leukemia-4353. html. Accessed December 3, 2018.

A Multi-Center Study of Ibrutinib in Combination With Obinutuzumab Versus Chlorambucil in Combination With Obinutuzumab in Patients With Treatment nai&#776;ve CLL or SLL. clinicaltrials.gov/ct2/show/NCT02264574. Updated January 6, 2017. Accessed December 3, 2018.

Updates from the annual ASH meeting, December 2018.

Clinical: Chronic Lymphocytic Leukemia

ELOQUENT-3: Adding Elotuzumab to Pomalidomide, Dexamethasone Improves PFS in R/R Multiple Myeloma

ELOQUENT-3 trial results show that adding elotuzumab to pomalidomide and dexamethasone improved progression-free survival (PFS) and overall response rate (ORR) in patients with multiple myeloma who had relapsed from or were refractory to (R/R) lenalidomide and a proteasome inhibitor. Results were presented December 1, 2018, at the 60th American Society of Hematology Annual Meeting & Exposition and previewed in the New England Journal of Medicine.

Immunomodulatory agents and proteasome inhibitors are the mainstay for treatment of multiple myeloma. Once patients relapse or become refractory, prognosis becomes extremely poor, with overall survival averaging 9 months. The triplet regimen of elotuzumab in combination with lenalidomide and dexamethasone, which combines an immunomodulatory agent with elotuzumab in patients with multiple myeloma who have progressed after at least 1 previous therapy, was approved in 2015.

Elotuzumab is a humanized monoclonal antibody that binds to signaling lymphocytic activation molecule F7 (SLAMF7) on the surface of myeloma cells and natural killer cells to initiate natural killer cell—mediated cellular cytotoxicity or macrophage-mediated killing on myeloma cells. Because pomalidomide also affects the immune system, investigators said that a combination of elotuzumab and pomalidomide will work synergistically and enhance cell-mediated killing of myeloma cells. In the phase 2 ELOQUENT-3 study, the efficacy and safety of elotuzumab plus pomalidomide and dexamethasone were compared with pomalidomide and dexameth- asone in patients with relapsed/refractory multiple myeloma who had already received lenalidomide and a proteasome inhibitor.

Patients who were relapsed/refractory to lenalidomide and a proteasome inhibitor were randomized in a 1:1 ratio to receive either elotuzumab plus pomalidomide and dexamethasone (elotuzumab group) or pomalidomide and dexamethasone (control group). Median PFS was 10.3 months in the elotuzumab group compared with 4.7 months in the control group (HR, 0.54; 95% CI, 0.34-0.86; 

 = .008). The addition of elotuzumab was beneficial across all key patient subgroups, including patients who had received at least 4 previous lines of therapy and patients with at least 1 cytogenetic abnormality (eg, chromosome 17p deletion). ORR was also higher in the elotuzumab group (53%) than in the control group (26%), with 20% of patients in the elotuzumab group having a very good partial response or better compared with 9% in the control group. Median duration of response was not reached in the elotuzumab group; it was 8.3 months in the control group.

Reported adverse events (AEs) were similar between the 2 groups. The most common grade 3-4 AEs in the elotuzumab group and control group, respectively, were neutropenia (13% vs 27%), anemia (10% vs 20%), infections (13% vs 22%), and hyperglycemia (8% vs 7%). AEs that led to discontinuation occurred in 18% of the patients in the elotuzumab group compared with 24% of the patients in the control group.

Elotuzumab in combination with pomalidomide and dexamethasone was shown to be effective and safe and can be considered for patients who have progressed after lenalidomide and a proteasome inhibitor.

Dimopoulos MA, Dytfeld D, Grosicki S, et al. Elotuzumab plus pomalidomide and dexamethasone for multiple myeloma. 

. 2018;379(19):1811-1822. doi: 10.1056/NEJMoa1805762.

Dangi-Garimella S. FDA’s decision on elotuzumab further expands options in multiple myeloma. 

website. ajmc.com/newsroom/fdas-decision-on-elotuzumab-further-expands-options-in-multiple-myeloma. Published November 30, 2015. Accessed December 14, 2018.

Carfilzomib-Based Combination Results in Sustained MRD-Negative Complete Response in Multiple Myeloma

Upfront treatment with carfilzomib, lenalidomide (Revlimid), and dexamethasone (KRd) with lenalidomide maintenance incorporating a “by-default-delayed” autologous stem cell transplant (ASCT) strategy in newly diagnosed multiple myeloma has demonstrated high rates of minimal residual disease negativity (MRD negative) complete response (CR).

Expanding on these results, researchers at the 60th American Society of Hematology Annual Meeting & Exposition, held December 1-4, 2018, in San Diego, California, presented long-term study results showing that these responses were sustained with a median duration of over 4 years among treatment-nai&#776;ve patients with multiple myeloma.

Following 8 cycles of KRd, patients received 2 years of lenalidomide 10 mg oral maintenance on days 1-21.

The primary objective of the study was to assess the rate of grade ≥3 peripheral neuropathy with secondary objectives of overall response rate (ORR), MRD negative CR, time to progression, and response duration assessed after every cycle during induction and subsequently after every 90 days of maintenance therapy. MRDneg CR was assessed by multi-color flow cytometry after 8 cycles of induction, 1 and 2 years of lenalidomide, and then annually.

Median potential follow-up was 5.7 years. The ORR was 97.8% (95% CI, 88.2%-99.9%) with a median duration of response of 65.7 months (95% CI, 55.6-not reached months). Notably, 28 patients (62.2%) had deep responses of MRD negative CR, and the durability was observed up to at least 70 months with a median duration of over 4 years.

Median time to progression was more than 5.5 years and median overall survival was not reached. However, at 80 months, 84.3% of patients were still alive. “As expected, patients who attained MRDneg CR by cycle 8 had a 78% reduction in the risk of progression,” wrote the researchers.

They added that these deep responses of MRD negative CR and long progression-free durations occurred regardless of age or cytogenic-based risk profile. Toxicities were generally manageable with no grade ≥3 neuropathy or death due to toxicity.

Kazandijan D, Korde N, Mailankody S, et al. A phase 2 study of carfilzomib, lenalidomide, and dexamethasone with lenalidomide maitenance (KRd-r) in newly diagnosed multiple myeloma (NDMM): sustained long term deep remissions and prolonged progresion-free duration regardless of age or cytogenetic risk after 5 years of follow up. In: Proceedings from the American Society of Hematology; December 1-4, 2018; San Diego, CA. Abstract 1957.

Clinical: Multiple Myeloma

Ruxolitinib Results in Better Treatment Response, Less Toxicity in Early Primary Myelofibrosis

For the first time, a study has demonstrated that early primary myelofibrosis (PMF) represents a category of patients who are likely to have better responses and lower toxicities from treatment with ruxolitinib. According to the study, led by Francesca Palandri, MD, PhD, of the Institute of Hematology at the University of Bologna, Italy, presented at the 60th American Society of Hematology Annual Meeting & Exposition, held December 1-4, 2018, in San Diego, California, a World Health Organization (WHO)—defined diagnosis may help better identify patients who may need strict monitoring during treatment with ruxolitinib (Jakafi).

In 2016, WHO criteria labeled early PMF as an individual entity with different clinical and laboratory presentations, as well as a significantly better outcome compared with overt PMF. However, there is a lack of information on the therapeutic effects of ruxolitinib depending on treatment setting.

Aiming to provide data on the differences in baseline clinical and laboratory characteristics, response to treatment, and toxicity between early and overt PMF treated with ruxolitinib, researchers utilized a clinical database in 23 European hematology centers. The database included retrospective data of 537 patients with myelofibrosis (MF) treated with ruxolitinib between January 2011 and July 2018. Spleen and symptom response were documented, and hematologic toxicity and infections were graded.

Of the 199 patients, 59 had a diagnosis of early PMF and 140 had a diagnosis of overt PMF. Median time from diagnosis to ruxolitinib initiation was 22.4 months.

Compared with patients with overt PMF, patients with early PMF started ruxolitinib with higher hemoglobin levels (median, 11.6 vs 10.4 g/dL) and lower circulating blast counts. They were also more frequently at intermediate-1 Dynamic International Prognostic Scoring System risk (69.6% vs 42.5%). The ruxolitinib starting doses and 12-week titrated doses were comparable between the 2 groups.

At 3 months, 43.1% of patients with early PMF achieved a spleen response, and at 6 months 48.9% achieved a spleen response, compared with 27.9% and 31.3% of patients with overt MF respectively. The rate of symptom response was also higher among patients with early PMF at both 3 months (82.5% vs 68.8%) and 6 months (90.0% vs 73.7%).

Toxicities and infections also favored patients with early PMF. In the first 12 months from ruxolitinib initiation, anemia and thrombocytopenia of all grades were observed in 75.6% and 43.1% in patients with overt PMF and in 86.3% and 60.0% of patients, respectively, with early PMF.

At 3 months, anemia was more prevalent among patients with overt PMF (94.7% vs 80.0%), with 32.6% of these patients having grade 3-4 anemia compared with 17.8% in early PMF. Similarly, rates of thrombocytopenia were also higher among patients with overt PMF at 3 months (51.5% vs 36.2%) and at 6 months (52.9% vs 35.8%), with only 2.2% and 2.5% of patients having grade 3-4 thrombocytopenia, respectively.

During treatment, 75 patients had at least one grade 2 or greater infectious episode. Overall, 108 patients discontinued treatment (52.5% of patients with early PMF and 55% of patients with overt PMF). Evolution into acute leukemia occurred in 21 patients.

Overall survival and progression-free survival were comparable between the 2 groups.

Myelofibrosis Survival After Discontinuing Ruxolitinib Differs Based on Reason for Discontinuation

Palandri F, Palumbo G, Abruzzese E, et al. Presentation and outcome of 199 patients with 2016 WHO diagnosis of early and overt primary myelofibrosis treated with ruxolitinib. In: Proceedings from the 60th American Society of Hematology Annual Meeting & Exposition; December 1-4, 2018; San Diego, CA. Abstract 3052.

Ruxolitinib (Jakafi) is the only targeted therapy available for the treatment of myelofibrosis (MF)-related splenomegaly and symptoms, and although 50% of patients with MF achieve significant clinical responses with ruxolitinib, half the responders stop responding over time.

Following failure with ruxolitinib, there are limited treatment options available. Among patients who fail on the treatment, prognosis is unfavorable, particularly among those who started ruxolitinib with advanced-stage disease, according to study results presented at the 60th American Society of Hematology Annual Meeting & Exposition held in San Diego, California.

The results further indicated that discontinuation because of disease evolution into acute leukemia or because of occurrence of a second solid neoplasia significantly reduced life expectancy.

The researchers assessed retrospective data from a clinical database created in 23 European hematology centers. The data included information on 537 patients treated with ruxolitinib from January 2011 to July 2018; information on 442 patients available as of July 15, 2018, was reported.

Spleen and symptom response to treatment were evaluated, and ruxolitinib-related toxicity and infections were graded. Overall survival was estimated from the date of ruxolitinib discontinuation to the date of death or last contact.

After a median follow-up of 30.5 months, 214 of the 442 (48.4%) evaluable patients discontinued ruxolitinib. Among these patients, (20.1%) died while on therapy because of MF progression (34.9%), infection (25.6%), heart disease (16.3%), second neoplasia (7%), hemorrhages (7%), and other causes (9.2%). Among the remaining 171 patients who discontinued ruxolitinib, median follow-up was 11.3 months. Reasons for discontinuation included drug-related toxicity (28.6%), loss or lack of response (23.4%), MF progression (12.3%), acute leukemia (13.4%), allogeneic stem cell transplantation (ASCT) (11.1%), second solid neoplasia (4.1%), and other unrelated causes (7.1%). 

After discontinuing ruxolitinib, 68 patients received 1 line of therapy, 21 received 2 lines, and 9 received more than 2 treatments. Additionally, 73 patients did not receive any therapy. Treatments received after ruxolitinib discontinuation, alone or in combination, included hydroxyurea, ASCT, second-generation JAK2 inhibitors, splenectomy, azacytidine/decitabine, chemotherapy, investigational agents, danazole, and erythropoietin-stimulating agents.

A total of 95 patients died following ruxolitinib discontinuation due to MF progression (30.5%), acute leukemia (25.4%), infections (14.7%), second neoplasia (9.5%), hemorrhages (4.2%), heart disease (4.2%), ASCT (4.2%), thrombosis (2.1%), and other causes (5.2%). Median survival time following ruxolitinib among the 171 patients was 22.6 months.

Survival following discontinuation was significantly influenced by Dynamic International Prognostic score category, transfusion dependency, and driver mutation status at baseline.

While receiving therapy, 45 of 153 (29.4%) and 123 of 161 (76.4%) evaluable patients achieved a spleen and symptoms response at any point, but survival was not affected by the previous response to treatment. However, survival significantly varied based on the reason for stopping treatment, with those discontinuing because of acute leukemia evolution or second solid neoplasia having the worst outcome.

Among patients who discontinued treatment in chronic phase, the use of second-generation tyrosine kinase inhibitors and other investigational agents prolonged survival compared with administration of conventional treatments.

Palandri F, Elli E, Polverelli N, et al. Outcome of patients with myelofibrosis after ruxolitinib failure: role of disease status and treatment strategies in 214 patients. In: Proceedings from the 60th American Society of Hematology Annual Meeting & Exposition; December 1-4, 2018; San Diego, CA. Abstract 4277.

Updates from annual ASH meeting, December 2018.

Clinical: Myelofibrosis

CT-P10 Is Similar to Reference Rituximab in Previously Untreated Advanced Follicular Lymphoma

At the 60th American Society of Hematology’s Annual Meeting & Exposition in San Diego, California, held December 1-4, 2018, researchers presented data from an ongoing randomized, double-blind trial comparing the efficacy of CT-P10 (Truxima)—a newly approved rituximab biosimilar&mdash; with reference rituximab (Rituxan) in patients with previously untreated advanced follicular lymphoma.

The study enrolled 140 patients, 124 patients of whom completed the full 8 cycles of rituximab, cyclophosphamide, vincristine, prednisone (R-CVP) induction therapy.

 In total, 122 patients who showed response during the induction period (62 patients in the CT-P10 treatment arm and 60 patients in the reference arm) then moved on to the maintenance period, during which 12 cycles of rituximab monotherapy were administered at intervals of 2 months.

Efficacy was determined based on outcomes including progression-free survival, duration of response, and overall survival (OS). The updated safety profile of CT-P10 compared with reference rituximab in advanced follicular lymphoma was also assessed. The study was designed to continue until death or up to 3 years from the randomized date of the last patient.

At the time of the cutoff date, the median follow-up was 23 months (range, 0.5-34) in the CT-P10 group and 22 months (range, 0.2-33) in the reference rituximab group. The rates of relapse, disease progression, or death from any cause were 22.9% and 24.3% for the CT-P10 and reference rituximab groups, respectively.

As for sustained response, the proportion of patients who showed relapse or disease progression after previously achieving overall response was 19.4% in the CT-P10 arm and 21.3% in the reference arm. Notably, there was no statistically significant difference in OS between either group with a 2-year OS of 93.2% for CT-P10 patients and 95.3% in reference rituximab patients.

Furthermore, “The updated safety results did not reveal any new trends or new signals noted in the patients treated with CT-P10,” a Celltrion representative said in an email.

The study’s authors concluded that, at the median follow-up of 23 months, the data demonstrated comparable progression-free survival, sustained response, and OS between both the biosimilar and the reference product.

FDA approved CT-P10 on November 28, 2018, under the brand name Truxima, though a launch date has yet to be disclosed.

 “Celltrion and Teva Pharmaceutical Industries entered into an exclusive partnership in October 2016 to commercialize Truxima in the United States and Canada. Teva and Celltrion have reached a settlement agreement with Genentech, including entry terms. The terms and conditions of that agreement are confidential at this time,” noted Woosung Kee, CEO of Celltrion.

Won-Seog, K, Buske C, Kwak L, et al. Similar efficacy and safety of CT-P10 and reference rituximab in patients with advanced stage follicular lymphoma: updated phase III study results. Presented at the 60th Annual Meeting and Exposition of the American Society of Hematology; December 1-4, 2018; San Diego, California. Abstract 1616. ash.confex.com/ash/2018/webprogram/Paper112716.html.

FDA approves first biosimilar for treatment of adult patients with non-Hodgkin’s lymphoma [press release]. Silver Spring, MD: FDA newsroom; November 28, 2018. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm627009.htm. Accessed December 4, 2018.

Longer-Term JULIET Results Confirm Sustained Response With Tisagenlecleucel in Relapsed/Refractory DLBCL

A median 19-month follow-up of the JULIET trial—a single-arm, open-label, multicenter, global, pivotal phase 2 trial of the chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel directed against CD19-expressing B cells&mdash;has found a 40% complete response (CR) and a manageable safety profile in adult patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

Tisagenlecleucel (Kymriah) was FDA approved in May 2018 for the treatment of adult patients with R/R large B-cell lymphoma following at least 2 prior line of therapy.

Conducted across 27 sites in 10 countries, the JULIET trial enrolled 167 patients with R/R DLBCL at the cutoff date of May 21, 2018, and 115 of them received an infusion of CD19-directed CAR T cells (dose range 0.1 x 108 to 6 x 108 cells). Eligibility criteria included at least 18 years of age; at least 2 lines of prior therapy, including an anti-CD20 antibody and an anthracycline; and were ineligible for or had failed autologous stem cell transplant (ASCT). Primary trial endpoint was overall response rate (ORR), as a sum total of the CR and partial response as assessed by an independent review committee. Secondary endpoints included duration of response (DOR), overall survival (OS), and safety.

About 90% of infused patients received bridging therapy and 93% received lymphodepleting chemotherapy. Median time from infusion to data cutoff was 19.3 months. Median age was 56 years (range, 22-76 years); 23% were aged ≥65 years. At study entry, 77% of infused patients had stage III/ IV disease; 55% and 43% had germinal center and activated B-cell molecular subtypes, respectively. More than half of the patients had received at least 3 prior lines of antineoplastic therapy (range, 1-6) and about the same number had undergone a prior ASCT.

Of the 99 patients who were evaluated who had at least 3 months of follow-up, ORR was 54% (95% CI, 43%-64%), with 40% CR. Further, ORR was consistent across prognostic subgroups that were evaluated, including prior ASCT, gender, age, and molecular subtype.

Median DOR was not reached at the time of data analysis, and DOR was not influenced by age or R/R status, the study found. No relapses were observed beyond 11 months after infusion. The median OS for all infused patients was 11.1 months (95% CI, 6.6 months-not evaluable [NE]) and was not reached for patients in CR (95% CI, 21 months-NE). The

OS probability was 48% (95% CI, 38%-57%) at 12 months and 43% (95% CI, 33%-53%) at 18 months, and, similar to DOR, was not influenced by the patient’s age or R/R status.

“These findings are consistent with what we’ve shown in our single-site studies here at Penn, which is that the majority of patients who go into remission stay in remission,” said Stephen J. Schuster, MD, director of the Lymphoma Program at the Abramson Cancer Center of the University of Pennsylvania, who is the principle investigator for the JULIET trial.

The authors compared the survival curves from their current study with those of the SCHOLAR-1 study

 and they found that patients enrolled in JULIET performed much better in terms of OS. The OS probability was about 30% and 25% for SCHOLAR-1 and CORAL at 12 months, respectively, and 25% and 20% at 24 months, respectively.

More than half (57%) of patients experienced cytokine release syndrome, 34% of which were grade 3/4. Prolonged (>28 days) cytopenias were observed in 45% patients, 34% of which were high-grade (3/4); a majority (17%) of infections in 37% of patients were grade 3. Twenty percent of treated patients experienced neurological adverse events, including a single case of grade 2 cerebral edema, which was detected without a contrast computed tomography (CT) scan, which disappeared following a contrast CT scan after 24 hours.

The authors report that there were no treatment-related deaths following their last data presentation at the Congress of the European Hematology Association in June 2018.

Schuster SJ, Bishop MR, Tam C, et al. Sustained disease control for adult patients with relapsed or refractory diffuse large B-Cell lymphoma: an updated analysis of Juliet, a global pivotal phase 2 trial of tisagenlecleucel. In: Proceedings from the American Society of Hematology; December 1-3, 2018; San Diego, CA. Abstract 1684.

Global trial shows CAR T therapy can lead to durable remissions in non-Hodgkin’s lymphoma [press release]. Philadelphia, PA: Penn Medicine; November 30, 2018. newswise.com/articles/view/704664/?sc =dwhr&xy=10014716. Accessed December 4, 2018.

Crump M, Neelapu SS2, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800-1808. doi: 10.1182/blood-2017-03-769620.

Gisselbrecht C, Schmitz N, Mounier N, et al. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20(+) diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma. 

. 2012;30(36):4462-4469. doi: 10.1200/JCO.2012.41.9416.

Borchmann P, Tam CS, Ulrich Jager, et al. An updated analysis of Juliet, a global pivotal phase 2 trial of tisagenlecleucel in adult patients with relapsed or refractory (r/r) diffuse large b-cell lymphoma (DLBCL). In: Proceedings from the 23rd Congress of the European Hematology Association; June 14-17, 2018; Stockholm, Sweden. Abstract S799.

Clinical: Lymphoma

Length of Hospital Stay Key Driver of Costs Associated With CRS Following CAR T-Cell Treatment

Health resource utilization data gathered from the TRANSCEND-NHL 001 trial show that longer stays in the intensive care unit (ICU) have a significant impact on the cost of care due to cytokine release syndrome (CRS) following treatment with chimeric antigen receptor (CAR) T cells. Presenting the results of the study at the 60th American Society of Hematology Annual Meeting & Exposition, held December 1-4, in San Diego, California, was Tanya Siddiqi, MD, hematologist/oncologist with City of Hope, Duarte, California.

CRS is a significant adverse effect of CAR T treatment. According to David Porter, MD, of the University of Pennsylvania Health System, T cells that have been activated release cytokines that activate other immune cells; this in turn releases more cytokines into the bloodstream. Consequently, the patient can experience high fever, severe flu-like symptoms, and other complications. This potentially fatal syndrome may require use of vasopressors, medications to improve blood pressure, and patients may need to be cared for in an ICU, Porter told 

Although symptoms may vary based on the type of CAR T-cell treatment being administered, the TRANSCEND-NHL 001 phase 1 study is evaluating lisocabtagene maraleucel (liso-cel), comprising CD19-directed 4-1BB CAR T cells, in adult patients with relapsed/ refractory diffuse large B cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma, follicular lymphoma Grade 3B, and mantle cell lymphoma.

“Resource use [in CRS management] may differ by product and remains to be evaluated,” Siddiqi said. “We have tried to estimate the cost of CRS management in relapsed/refractory DLBCL,” she said, adding that their analysis focused on dose-finding and dose-expansion cohorts from the trial. 

Participants were infused with 1 or more cycles of liso-cel, which includes lymphodepletion followed by 1 or 2 doses of the CAR T-cell infusion. The trial has a follow-up period of 24 months following the first infusion.

The authors looked at the case report forms of patients who experienced CRS to evaluate the health resource utilization (HRU) associated with CRS management, which was assessed using a 2-step micro-costing method.

 “Data cut-off was May 4, 2018,” Siddiqi said. In the first step, she explained, they analyzed HRU for managing each event, including number of inpatient days, number of ICU days, procedures, and medications.

“HRU was included if it was within the protocol management guidelines,” she added. The analysis included HRU that occurred within the onset date and resolution date of a treatment-related adverse event. In the second step, cost was attributed to each HRU, which included diagnostic and laboratory testing; hospitalization, procedures, and office visits; and medication costs.

“Our methods were consistent with previous microcosting efforts in CAR T adverse event management conducted by the Institute for Clinical and Economic Review,” Siddiqi said.

Analyses were stratified by grade and by site of care (eg, inpatient or outpatient), where the CAR T-cell therapy was administered.

The researchers used the Lee criteria5 for grading CRS, which clustered a majority of patients in the current cohort in grade 1 and grade 2. Of the 38 (out of 102) patients treated in the dose-finding/dose-expansion portions of the trial who experienced CRS, 19 (19%) patients experienced grade 1 symptoms, 18 (18%) grade 2, and 1 patient had grade 4 CRS. Total HRU and cost varied based on CRS grades. A higher grade of CRS, not surprisingly, was associated with a longer length of stay (LOS): The mean LOS for grades 1 and 2 were 4 and 7 days, respectively, for inpatient CAR T administration. One patient with grade 4 had a LOS of 34 days. Among those who received outpatient CAR T-cell treatment, the mean LOS was 2 days for grade 1 CRS and 6 days for grade 2 CRS. Patients in the inpatient setting had longer mean LOS compared with those in the outpatient setting. Although patients with grade 1 CRS did not need ICU admission, the mean ICU LOS for CRS grade 2 patients was 1 day, and 1 patient was in the ICU for 26 days.

Siddiqi highlighted that patients were successfully managed with conservative HRU compared with the trial’s recommended guidelines. Only half (9/18) who experienced grade 2 CRS were administered the recommended tocilizumab, she said.

The analyses found that hospitalization had the most impact on overall cost, which was much lower for patients who experienced grade 1 ($11,226) and grade 2 ($25,617) CRS. Hospitalization costs alone were $10,813 and $21,397, respectively. The lone patient with CRS grade 4 who had a 34-day LOS, 26 of which were spent in the ICU, incurred an estimated total cost of $201,836.

“More so than diagnostics and drugs, hospitalization led to a tremendous cost burden,” Siddiqi said. The 1 outlier was her own patient, who came in with a large disease burden to start with, and he had CRS as well as neurotoxicity, which is another adverse effect of CAR T-cell treatment. He was on a ventilator as well.

Resource use not referenced in the guidelines was largely made up of medication use and resulted in minimal increases in total cost. These costs ranged from $1698 (grade 1) to $21,055 (grade 4).

Siddiqi highlighted certain limitations of the study, including that grade 3/4 events are not well represented in their cohort. Additionally, CRS definitions, management, and incidence vary across CAR T-cell therapies, and costs were derived from national averages and may not be generalizable across institutions.

She concluded that based on the analysis, hospital and ICU LOS seem to be key drivers of CRS management cost and are mainly associated with managing higher-grade CRS. Siddiqi noted, however, that although actual costs may vary between hospitals, CRS management guidelines, which vary across CAR T therapies, will significantly affect both HRU and associated cost differences.

“Improvement of CAR T-cell therapy complications may be achieved through efficient intervention strategies and product engineering,” to reduce the incidence and the grade of CRS, Siddiqi said.

Siddiqi T, Garcia J, Dehner C, et al. Estimation of the resource utilization and costs of cytokine release syndrome observed in the Transcend-NHL clinical trial: a micro-costing study. In: Proceedings from the American Society of Hematology; December 1-3, 2018; San Diego, CA. Abstract 319. ash.confex.com/ash/2018/webprogram/Paper112214.html.

Dr David L. Porter discusses side effects of CAR T-cell therapy. 

 website. ajmc.com/interviews/dr-david-l-porter-discusses-side-effects-of-car-t-cell-therapy. Published April 11, 2017. Accessed December 2, 2018.

Study Evaluating the Safety and Pharmacokinetics of JCAR017 in B-cell non-Hodgkin Lymphoma (TRANSCEND-NHL-001). clinicaltrials.gov/ct2/show/NCT02631044. Updated October 12, 2018. December 2, 2018.

Resource use management: principles 6-10. Global Health Cost Consortium website. ghcosting.org/pages/standards/principles/resource_use_measurement.

Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release syndrome [erratum in Blood. 2015;126(8):1048]. Blood. 2014;124(2):188-195. doi: 10.1182/blood-2014-05-552729.

Studies at ASH Evaluate Episodic ED Utilization, Adherence, QOL in Sickle Cell Disease

Patients with sickle cell disease (SCD) typically have episodic emergency department (ED) and inpatient encounters, and innovative interventions are necessary to improve adherence

to hydroxyurea (HU) treatment among youth suffering from SCD. These were the findings of 2 studies presented during an outcomes research session December 1, 2018, at the 60th American Society of Hematology (ASH) Annual Meeting & Exposition, held in San Diego, California.

ED utilization and inpatient admission among patients with SCD are known issues, but utilization can vary among individual patients. A 30-month study that involved 427 patients in 2 institutions in North Carolina, for example, found that 1 cohort of patients with SCD had more hospital admissions and ED encounters while the other cohort had more day hospital encounters.

 Pain associated with SCD is a common reason for ED visits.

The first study, presented at the ASH annual meeting by Susan Paulukonis, MA, MPH, program director, California Rare Disease Surveillance Program, evaluated both high-use and quiescent periods among patients seen in California’s nonfederal hospitals over 12 years.

“We were seeing peaks and valleys of ED utilization, and we wanted to understand those patterns better,” Paulukonis said.

The data are part of the California Sickle Cell Data Collection project, a statewide effort to use a wide range of administrative, clinical, and other data sources to describe the population living with SCD, their health outcomes, and healthcare utilization patterns. Paulukonis shared analyses of data gathered from inpatient and ED encounters (with or without an associated inpatient stay) from 2005 to 2016. Patient identifiers across data set and year helped link the patient information. A true SCD case was defined as 3 or more occurrences of a SCD-specific International Classification of Diseases code (version 9 or 10) within any 5-year period between 2005 and 2016. Patients who met this definition and had at least a 1-year follow-up were included in the analyses.

Quiescent periods were defined as lengths of time in which a person had zero or near-zero encounters in ED or inpatient settings. Occasional and high-use periods of ED utilization were quantitatively defined by the model.

“Among the 5090 patients who qualified for the study, the median follow-up period was 9.8 years, with a range of 1.0 to 11.0 years. There were over 94,000 stand-alone ED encounters, while over 59,000 ED encounters were associated with an inpatient stay,” Paulukonis said when describing the cohort that was analyzed.

A 3-component model was used to combine predictive power, parsimony, and clinical relevance, including quiescent periods (mean, 0.09 encounters; 88.8% of 4-week periods), occasional-use periods (mean, 1.28 encounters; 10.8% of 4-week periods), and high-use periods (mean, 7.48 encounters; 0.5% of 4-week periods).

All but 2 patients experienced at least 1 quiescent period during the study period, 75.9% experienced at least 1 occasional-use period, and 8.0% experienced at least 1 high-use period. According to Paulukonis, patient age did not influence the occasional- or high-use periods, which lasted a median of 8 weeks; 3.6% of these spells included at least some very high-use. Younger patients (<20 years) had longer durations of quiescent periods compared with older (≥20 years) patients (median, 24 vs 16 weeks, respectively).

Paulukonis concluded that most patients with SCD experience discrete periods during which ED and inpatient hospital encounters are not uncommon, separated by somewhat longer periods with few encounters or none. Additionally, younger patients are more likely to experience these high-frequency episodes. “We will try to tease out if, based on a patient’s status at a particular time, what will happen to the patient 2, 4, or 6 months from that time,” Paulukonis said.

Further research will include determining the likelihood of change in state for a given patient based on history and prior state. Additionally, the researchers plan to identify whether health events or patient characteristics are associated with occasional or high-use states.

Another presentation during the same session evaluated the impact of treatment adherence to HU on the quality of life (QOL) in younger patients with SCD. Adherence issues persist among younger patients

 receiving HU for SCD, and behavioral interventions are currently being tested in the field. The study

 was presented by Arlene Smaldone, PhD, CPNP-PC, CDE, Columbia University School of Nursing and College of Dental Medicine, New York, New York, and her colleagues.

The researchers examined barriers to HU adherence from the perspective of the sampled youth and their parents; these were poorly adherent youth aged 10 to 18 years and their parents who participated in the Hydroxyurea Adherence for Personal Best in Sickle Cell Disease (HABIT) trial, which had a 6-month intervention. In addition to self-reported barriers to HU at 0, 3, and 6 months following treatment initiation, the researchers evaluated the association between adherence and generic and disease-specific health-related QOL (HRQOL) markers. Further, the study examined whether a community health worker could reduce adherence barriers, and if so, how.

January 2019

Clinical: CAR T-Cell Therapy

Clinical: Chronic Lymphocytic Leukemia

Clinical: Multiple Myeloma

Clinical: Myelofibrosis

Clinical: Lymphoma

Cost of Care

Cost of Care: Biosimilars

Quality of Life

Policy

AJMCtv® Interviews, January 2019