Featuring abstracts from the Association of Community Cancer Centers, US Oncology, City of Hope, and Florida Cancer Specialists & Research Institute.
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:
References
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 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
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:
Cost of care data underscore the burden of grade ≥ 3 HAEs:
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
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