ASH 2021 Recap: Research From Our Partners

ACCC Presents Survey Responses on Adoption of Bispecific Antibodies

Bispecific antibodies have been big news in the world of hematology for some time, ever since the 2014 approval of the first such therapy, blinatumomab, which targets both CD19 on the surface of B-cell lymphoblasts and CD3 on the surface of T cells.¹ The 2-for-1 punch of these novel immunotherapies can overcome limitations of conventional monoclonal antibodies.

In 2020, the Association of Community Cancer Centers (ACCC) created an ongoing education program to identify and address barriers to adoption of bispecific antibodies for the treatment of hematological malignancies. For this program, ACCC created a survey to better understand multidisciplinary cancer providers’ experiences with these therapies, with a focus on experiences with blinatumomab. Results of the survey were presented in an abstract during the 2021 American Society of Hematology Meeting & Exposition.²

According to the abstract, the survey received 129 individual responses, with 66% of those reporting that they prescribed, dispensed, and administered blinatumomab and/or cared for patients being treated with it. Of these, 44% were medical oncologists/hematologists, 8% were advanced practice providers (APPs), 17% were nurses, 23% were pharmacists, and 9% fell into an “other” category of various other disciplines.

Provider experiences with blinatumomab varied; 92% of oncologists had experience with blinatumomab while only 35% of nurses reported this. Regarding community use, respondents said 59% of their institutions use it to treat relapsed or refractory acute lymphoblastic leukemia (ALL) and 41% use it to treat ALL with minimal residual disease positivity. Of note, 74% of oncologists said they use blinatumomab before chimeric antigen receptor T-cell therapy when deciding between the 2 options for patients with ALL.

The survey also found:

• 79% of providers are comfortable caring for patients treated with blinatumomab, but 59% identified barriers when caring for these patients.
• Challenges include transitioning patients from the inpatient to outpatient setting (41%), managing patients who live in remote areas (33%), securing insurance coverage (28%), managing adverse events (27%), helping patients address financial costs, (24%), and lacking in-house expertise with the drug (22%).
• Managing neurotoxicity and cytokine release syndrome was also reported as a challenge. Fewer than half of oncologists reported experience in this area, and only 6% to 9% of APPs reported having experience. Of note, 23% of nurses did not feel they had all the information needed to safely administer blinatumomab.
• 86% of respondents said written guidelines, best practices, and care recommendations would help. Requested resources included a list of home health pharmacies and agencies familiar with blinatumomab, care coordinators or navigators, best practices on care transitions, and information on outpatient administration.
• Expertise from the drug manufacturer and direct patient education were seen as beneficial, and 70% thought that peer support services for patients would also be helpful.

References

1. Mullard A. FDA approves first bispecific. Nat Rev Drug Discov. 2015;14(7). doi:10.1038/nrd4531
2. Atembina L, Boehmer L, Terrell K, et al. Multidisciplinary provider insights to promote adoption of bispecific antibodies to treat cancer in the community. Presented at: 63rd American Society of Hematology Meeting & Exposition; December 11-14, 2021; Atlanta, GA. Abstract 4033. https://ash.confex.com/ash/2021/webprogram/Paper153794.html

Phase 1 Study in R/R Hodgkin Lymphoma Shows Significant Responses to Pembrolizumab Plus Oral Vorinostat

Phase 1 results presented at the 2021 American Society of Hematology Meeting & Exposition show that adult patients with relapsed or refractory (R/R) Hodgkin lymphoma (HL) who were transplant ineligible had significant responses to intravenous pembrolizumab taken with oral vorinostat, a histone deacetylase (HDAC) inhibitor.

In preclinical studies, HDAC inhibitors have been shown to have immunomodulatory effects— including enhancing antigen presentation, recruiting T cells into tumors, and promoting T-cell function—when combined with PD-1 inhibitors, according to investigators from City of Hope, led by Alex F. Herrera, MD.

Oral vorinostat (Zolinza; Merck) is being studied with pembrolizumab in R/R HL as well as in diffuse large B-cell lymphoma and follicular lymphoma. Herrera reported on the phase 1 results involving 32 patients with R/R HL.

According to the abstract, these patients were heavily pretreated. The median number of prior therapies was 4 (range, 2-12), with 94% having had prior brentuximab vedotin, with 66% refractory; 78% had prior PD-1 blockade, with 56% refractory to PD-1 inhibition. At baseline, 75% had stage III-IV disease; 69% were male and 72% were White, with a median age of 35 years (range, 18-79).

Study design. Patients were treated in a dose-escalation cohort with 2 dose levels (DLs) using a Rolling 6 design, followed by an expansion cohort with treatment at the recommended phase 2 dose. At the first DL, vorinostat was given orally at 100 mg a day for days 1 to 5 and 8 to 12; at the phase 2 DL, patients received 200 mg a day of vorinostat on days 1 to 5 and 8 to 12. The pembrolizumab doses were 200 mg intravenously every 3 weeks on both DLs. Treatment continued for a maximum of 2 years. Primary end points were safety and the determination of response to the phase 2 dose.

Safety results. The median number of cycles was 8.5 (range, 1-36). The most common adverse events (AEs) were hypertension (72%), fatigue (63%), hyponatremia (63%), nausea (63%), diarrhea (47%), thrombocytopenia (44%), and anemia (41%). The most common AEs of grade ≥3 included hypertension (9%), neutropenia (6%), thrombocytopenia (6%), hypophosphatemia (6%), and lymphopenia (6%). Immune-related AEs included with grade 1-2 thyroiditis (four patients), grade 1 rash (one patient), and grade 3 esophagitis/duodenitis (one patient).

One patient had vorinostat dose reduction due to neutropenia. Twenty of 32 patients discontinued treatment: 11 due to disease progression, 6 due to stem cell transplant, 2 due to patient preference, and 1 due to completion of 2 years of therapy.

Responses. It was too early to evaluate the responses of 2 patients. For the 30 patients who could be evaluated, investigators reported the following results:

• The best overall response rate (ORR) was 73%; the complete response (CR) rate was 33%. Among patients who were naïve to anti–PD-1 agents or sensitive to them, the ORR was 93% and the CR rate was 64%. Among patients who were refractory to prior PD-1 therapy, the ORR was 56% and CR was 6%.
• Ten evaluable patients were anti-PD1 refractory patients with PD1 blockade as their most recent therapy prior to the study, and all had partial responses.
• Median follow-up time in 28 surviving patients was 28 months (range, 1-41).
• Patients had 1-year progression-free survival (PFS) of 52% and an overall survival (OS) of 93%.
• Median duration of response, PFS, and OS in all R/R HL patients were 14 months, 14.9 months, and not reached, respectively.

The investigators concluded, “Pembrolizumab and vorinostat was tolerable and produced a high ORR and CR rate in patients with anti–PD-1 naïve/sensitive R/R HL. A majority of patients with anti–PD-1 refractory R/R HL had objective responses, including patients who had progressed while receiving PD-1 blockade as their most recent therapy.” 

Reference

Herrera AF, Chen L, Budde LE, et al. Pembrolizumab plus vorinostat induces responses in patients with Hodgkin lymphoma who are refractory to prior PD-1 blockade. Presented at: 63rd American Society of Hematology Meeting & Exposition; December 11-14, 2021; Atlanta, GA. Abstract 234. https://ash.confex.com/ash/2021/webprogram/Paper150031.html

Blue Ridge Cancer Care’s Goldschmidt Presents Data on Managing Hematological Events

What is an abstract involving patients with small cell lung cancer (SCLC) doing at a meeting on hematology?

As Jerome Goldschmidt, MD, an oncologist at Blue Ridge Cancer Care, in Blacksburg, Virginia, explained, the findings aren’t about SCLC per se, but about managing common hematological adverse events (HAEs) that can occur when patients are treated with chemotherapy. Many patients experience anemia, neutropenia, and thrombocytopenia, and managing these events—or better yet, preventing them—is key to patients staying on the recommended dose of therapy and avoiding AEs that lead to costly hospital stays. (Blue Ridge Cancer Care is part of The US Oncology Network.)

Goldschmidt served as principal investigator for a retrospective, observational study conducted with Ontada, an oncology real-world data and evidence, clinical education and provider technology business of McKesson. Their findings were presented during the 2021 American Society of Hematology Meeting & Exposition.¹

Investigators used iKnowMed electronic health record data from January 1, 2015, through January 31, 2020, to identify patients for the study. Goldschmidt said that about 1400 patients fit the overall inclusion criteria, and patients were then divided into 2 groups: those who had experienced a grade ≥3 HAE and those who had not. Investigators found that 778 patients experienced a grade ≥ 3 HAE during that period. “That’s a majority of the patients,” Goldschmidt said in an interview with Evidence-Based Oncology™ during the meeting in Atlanta.

Digging deeper, the analysis showed that myelosuppression HAEs in extensive-stage SCLC bring a heavy burden in the community oncology setting. “We looked at the burden on patients, which translated into transfusions, missed doses, dose reductions, and lower dose intensity,” Goldschmidt said. All of these were higher in patients with grade ≥ 3 AEs.

Health care costs were higher, too. Goldschmidt noted that the study calculated the differences in outpatient costs only, and they were still substantial. “Our hypothesis was that there would be more health care utilization if you had these adverse events. And indeed, that’s what we showed,” he said.

Health outcomes data from the Ontada analysis showed the following:

• Of those patients with at least one grade ≥ 3 HAE after starting chemotherapy, 50.3% had grade 3 anemia, 46.0% had grade 3 neutropenia, 28.0% had grade 4 neutropenia, 33.8% had grade 3 thrombocytopenia, and 18.1% had grade 4 thrombocytopenia.
• Of the 778 patients with grade ≥ 3 HAEs, 454 (58.4%) had 2 or more types, and 12.2% had anemia, neutropenia, and thrombocytopenia.
• 43.1% of the patients were eligible for red-blood-cell infusion, and 3.9% for platelet infusion; 12.2% of patients had major bleeding events.
• Compared with patients who did not have grade 3 HAEs, those with grade ≥ 3 HAEs were more likely to have dose reductions (46.7% vs 32.2%, respectively); treatment holds (12.7% vs 5.9%); and treatment delays (92.3% vs 84.3%; all P < .001).

Cost of care data underscore the burden of grade ≥ 3 HAEs:

• Total outpatient costs within 12 months after the start of chemotherapy were higher for patients with vs without grade ≥ 3 HAEs ($37,613 vs $31,176; P = .004).
• Patients with grade ≥ 3 HAEs had an mean of 10.7 outpatient visits within 12 months of starting chemotherapy vs 7.7 outpatient visits for those without grade 3 HAEs (P < .0001).
• Patients with grade ≥3 HAEs had greater use of granulocyte colony-stimulating factor, more intravenous hydration, and greater use of erythropoiesis-stimulating agents, at higher costs.

Goldschmidt has studied the use of trilaciclib in this SCLC population. He coauthored an analysis of 3 related studies, which found that administering trilaciclib prior to chemotherapy reduces myelosuppression and improves health-related quality of life for these patients.²

“Pegfilgrastim and filgrastim are phenomenal drugs,” Goldschmidt elaborated, “but they do have their costs, their side effects, and their difficulties in delivery. Plus, they really only treat 1 cell line.” Newer therapies can prevent more hematological events in more cancers and are worth studying, he said.

“Future studies will address the benefits of trilaciclib from the standpoint of health economics, as well as relieving suffering from the patient’s end while on chemotherapy,” said Goldschmidt. “We’ll also look at how it interacts with immunotherapy,” as well as its potential benefits in other types of cancers, such as breast and colon cancer.

References

1. Goldschmidt JS, Monnette A, Shi P, Venkatasetty D, Huang H, Chioda M. Understanding hematological adverse event management through health care resource utilization, costs, and treatment patterns of patients with extensive-stage small cell lung cancer treated in the community oncology setting. Presented at: 63rd American Society of Hematology Meeting & Exposition, December 11-14, 2021; Atlanta, GA. Abstract 1913. https://ash.confex.com/ash/2021/webprogram/Paper148057.htm
2. Weiss J, Goldschmidt JS, Andric Z, et al. Effects of trilaciclib on chemotherapy-induced myelosuppression and patient-reported outcomes in patients with extensive-stage small cell lung cancer: pooled results from three phase II randomized double-blind, placebo-controlled studies. Clin Lung Cancer 2021;22(5):449-460. doi:10.1016/j.cllc.2021.03.010