Daratumumab regimen benefits Black patients with newly diagnosed multiple myeloma
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The addition of daratumumab to lenalidomide, bortezomib and dexamethasone benefitted Black patients with transplant-eligible newly diagnosed multiple myeloma, according to data presented at Society of Hematologic Oncology Annual Meeting.
The inclusion of daratumumab (Darzalex; Genmab, Janssen Oncology) in the induction and consolidation regimen improved depth of response, including rates of stringent complete response and minimal residual disease negativity.
The addition of daratumumab to lenalidomide (Revlimid, Celgene) maintenance therapy further improved depth of response, Ajay K. Nooka, MD, MPH, FACP, associate professor of hematology and medical oncology at Emory School of Medicine, and colleagues concluded.
“These results support [daratumumab, lenalidomide, bortezomib (Velcade, Takeda) and dexamethasone] as a potential new standard of care for Black patients with transplant-eligible newly diagnosed multiple myeloma,” Nooka said during a presentation. “Larger studies are needed to better define the magnitude of daratumumab benefit [for] Black patients.”
Daratumumab — a human immunoglobulin G1 kappa monoclonal antibody that binds to CD38 — is approved in the United States for several indications in multiple myeloma.
Randomized studies showed daratumumab-based regimens significantly improved response rates, depth of response and PFS among patients with newly diagnosed multiple myeloma, as well as those with relapsed or refractory disease.
The RVd regimen — which consists of lenalidomide, bortezomib and dexamethasone — followed by high-dose therapy, autologous stem cell transplant and consolidation is a standard regimen in the United States for newly diagnosed multiple myeloma.
The randomized phase 2 GRIFFIN study evaluated the addition of daratumumab to RVd for patients with newly diagnosed disease who were eligible for autologous stem cell transplant.
Researchers randomly assigned patients to RVd with daratumumab (n = 104) or without (n = 103).
All patients received four induction cycles, high-dose therapy, autologous stem cell transplant, two consolidation cycles, and 24 months of maintenance therapy.
During the 21-day induction and consolidation cycles, patients received lenalidomide dosed at 25 mg orally on days 1 to 14, subcutaneous bortezomib dosed at 1.3 mg/m2 on days 1, 4, 8 and 11, and 40 mg dexamethasone on days 1, 2, 8, 9, 15 and 16.
Patients assigned daratumumab received 16 mg/kg via IV on days 1, 8 and 15 of the induction cycles, and on day 1 of the two consolidation cycles.
During maintenance — administered in 28-day cycles — patients received 10 mg lenalidomide on days 1 to 21. If tolerated in the first 3 months, the dose was increased to 15 mg in months 4 through 24.
Those assigned daratumumab received 16 mg/kg via IV every 8 weeks during maintenance, or every 4 weeks per patient decision allowed after study amendment.
Stringent complete response by the end of consolidation per International Myeloma Working Group criteria served as the primary endpoint.
As Healio previously reported, results presented at last year’s ASH Annual Meeting and Exposition showed the addition of daratumumab to lenalidomide, bortezomib and dexamethasone significantly improved rates of stringent clinical response and minimal residual disease negativity in the overall study population.
Nooka and colleagues conducted a subgroup analysis to assess the efficacy of the regimen for Black patients (n = 32).
In this subgroup, 14 patients received daratumumab plus RVd and 18 patients received RVd alone. Baseline characteristics were balanced between treatment groups with regard to median age (58.5 years vs. 57 years), sex (male, 35.7% vs. 44.4%), cytogenetic risk (standard, 78.6% vs. 87.5%; high, 21.4% vs. 12.5%), ECOG performance status (0 or 1, 92.4% vs. 94.5%) and Multiple Myeloma International Staging System stage (stage I, 64.3% vs. 61.1%; stage II, 21.4% vs. 22.2%; stage III, 14.3% vs. 16.7%).
By the end of consolidation, Black patients who received daratumumab were significantly more likely than those who received RVd alone to achieve stringent complete response (71% vs. 33%; P = .0353) or achieve complete response or better (P = .0085).
Results showed response rates and depth of responses continued to improve at all time points for Black patients treated with daratumumab.
By the end of consolidation, a higher percentage of Black patients who received daratumumab plus RVd than RVd alone achieved minimal residual disease negativity at a level of 10-5 (36% vs. 17%).
The most common hematologic adverse events that occurred more frequently among Black patients who received daratumumab included neutropenia (any grade, 57% vs. 33%; grade 3/grade 4, 50% vs. 22%), anemia (any grade, 50% vs. 39%), leukopenia (grade 3/grade 4, 21% vs. 6%) and thrombocytopenia (any grade, 43% vs. 39%; grade 3/grade 4, 29% vs. 11%).
The most common nonhematologic adverse events that occurred more frequently among those who received daratumumab included upper respiratory tract infection (any grade, 71% vs. 44%), fatigue (any grade, 64% vs. 44%; grade 3/grade 4, 7% vs. 0%), constipation (any grade, 64% vs. 39%), nausea (any grade, 57% vs. 50%), peripheral edema (any grade, 57% vs. 50%), vomiting (any grade, 50% vs. 28%), cough (any grade, 50% vs. 22%), pyrexia (any grade, 50% vs. 17%) and insomnia (any grade, 50% vs. 17%).
In the subgroup of Black patients, treatment-emergent adverse events prompted 36% of those assigned daratumumab plus RVd and 28% of those assigned RVd alone to discontinue treatment. Thirty-six percent of patients assigned daratumumab plus RVd and 56% of those assigned RVd alone experienced serious adverse events; however, no patients died due to adverse events.
“The safety profile of [daratumumab plus RVd for] Black patients was generally consistent with that [among] white patients,” Nooka said. “Overall, improved recruitment of Black patients in clinical trials is needed to understand disease biology and response to therapy among racial groups.”
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Nooka AK, et al. Abstract MM-350. Presented at: Society of Hematologic Oncology Annual Meeting (virtual meeting); Sept. 9-12, 2020.
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