Daratumumab Leads to Deep Responses Among Newly Diagnosed Black Patients With Multiple Myeloma

Adding the anti-CD38 antibody, daratumumab (Darzalex), to the standard of care regimen of lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (D-RVd), improved depth of response, stringent complete response (sCR), and minimal residual disease (MRD) negativity, in a subgroup of Black patients who had newly diagnosed multiple myeloma, according to findings from an analysis presented at the eighth annual Society of Hematologic Oncology (SOHO) meeting on September 10, 2020.¹

“This analysis is not meant to provide a direct comparison between the Black or the White patients,” lead author Ajay K. Nooka, MD, MPH, Associate Professor, Department of Hematology and Medical Oncology at Emory University School of Medicine, said. “The intent is to determine if daratumumab can benefit patients who are African American or not,” he said.

The subgroup analysis sought to elucidate a greater understanding of the differences in outcomes for Black patients versus White patients based on primary analysis of the GRIFFIN (NCT02874742) study, said Nooka, who is also Medical Director at the Winship Cancer Institute of Emory University.² Historically, Black patients have had poorer outcomes than White patients, although, when given equal access to care, Black patients have similar or better outcomes relative to White patients.^3,4

In updated GRIFFIN findings, at the end of post-allogeneic stem cell transplant (post-ASCT), sCR favored D-RVd versus RVd at 42.4% versus 32.0%, respectively (odds ratio [OR]; 1.57; 95% CI, 0.87-2.82; 1-sided P = 0.068), meeting the prespecified 1-sided α of 0.10.

At a median of 22.1 months follow-up, deepening responses were observed, in addition to improved sCR rates for D-RVd versus RVd (62.6% vs 45.4%; P = 0.0177) and MRD-negativity rates in the intent-to-treat (ITT) population (51.0% vs 20.4%; P < 0.0001). The addition of the anti-CD38 antibody essentially doubled the likelihood of achieving sCR (OR, 1.98; 95% CI, 1.12-3.49; P = 0.0177).

The current subanalysis evaluated 32 Black patients who received either D-RVd (14 patients) or RVd (18 patients). Baseline characteristics such as age, cytogenetic risk profile, ECOG performance status, and International Staging System disease stage were similar between the 2 groups.

Nooka et al reported that the sCR rate was higher for Black patients who received D-RVd versus RVd (71% vs 33%) at the end of the consolidation phase. The OR was 5.00 (95% CI, 1.10-22.82; 2-sided P = 0.0353). Similar findings were reported in White patients, with higher sCR rates observed with the 4-drug regimen versus the 3-drug regimen (43% vs 34%, respectively). The odds ratio for sCR at the end of consolidation among White patients was 1.46 (95% CI, 0.76-2.82; P = 0.2620).

“By the end of the consolidation phase, the sCR rate was improved for D-RVd versus RVd in both patient populations,” Nooka said.

The overall response rate (ORR) was 100% and 94% for D-RVd and RVd, respectively, in Black patients, with similar findings reported for White patients (TABLE). “The responses deepened over time in both the Black patients and White patients with a complete response of 21% by the end of transplant, which increased to 86% by the end of consolidation, with 71% of these found to be stringent complete responses,” Nooka said. This improvement was observed for all time points among Black patients who received daratumumab.

By the end of posttransplant consolidation, MRD negativity at the 10-5 threshold was significantly higher in the daratumumab arm, 36% in D-RVd compared with 17% in RVd in Black patients. In White patients, MRD negativity was 49% in the D-RVd group compared with 16% in RVd group.

Regarding toxicities, the most common any grade treatment-emergent adverse events (TEAEs) in Black patients was neutropenia (57%), anemia (50%), leukopenia (43%), thrombocytopenia (43%), and lymphopenia (36%) for the D-RVd arm. In White patients, toxicity rates were similar with 58% experiencing neutropenia, followed by thrombocytopenia (45%), leukopenia (25%), anemia (34%), and lymphopenia (30%) for the D-RVd arm. The rate of grade 3 or 4 TEAEs in the D-RVd versus RVd arms was 79% versus 83% for Black patients, respectively, and 83% versus 76% for White patients. “Overall, higher rates of grade 3 and 4 neutropenia, leukopenia, and thrombocytopenia were observed for D-RVd in Black and White subgroups,” Nooka said.

The most common nonhematologic TEAEs among Black patients treated with D-RVd were upper respiratory tract infection, fatigue, and constipation.

Treatment discontinuation occurred in 36% and 28% of Black patients in the D-RVd and RVd arms, respectively, and in 11% and 16% of White patients. Among Black patients, 5 patients in each treatment arm discontinued lenalidomide, bortezomib, or dexamethasone with the most frequent cause attributed to peripheral neuropathy or neuralgia. Infusion-related reactions (IRRs) to daratumumab occurred in 29% of Black patients and 45% of White patients. Overall, IRRs were generally mild (grade 1 or 2). There were zero deaths reported for either subgroup. Overall, the safety profile of D-RVd among Black patients was consistent with White patients, Nooka said.

“In Black patients with newly diagnosed multiple myeloma, using D-RVd as induction and consolidation therapy improved depth of response, including the rate of sCR and MRD negativity,” Nooka said. “These results support D-RVd as a potential new standard of care for Black patients who are transplant eligible and newly diagnosed.”

“The responses deepened over time in both the Black patients and White patients with a complete response of 21% by the end of transplant, which increased to 86% by the end of consolidation, with 71% of these found to be stringent complete responses.” – Ajay K. Nooka, MD, MPH

_Reference:

_{1. Nooka AK, Kaufman JL, Rodriguez C, et al. Daratumumab + Lenalidomide/Bortezomib/Dexamethasone in African American/Black Patients With Transplant-eligible Newly Diagnosed Multiple Myeloma: Subgroup Analysis of GRIFFIN. Presented at: Eighth Annual Society of Hematologic Oncology meeting; September 9-12, 2020. https://soho.6connex.com/event/AnnualMeeting/login/​}

_{2. Voorhees PM, Kaufman JL, Laubach J, et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020;136(8):936-945. doi:10.1182/blood.2020005288}

_{3. Costa LJ, Brill IK, Omel J, Godby K, Kumar SK, Brown EE. Recent trends in multiple myeloma incidence and survival by age, race, and ethnicity in the United States. Blood Adv. 2017;1(4):282-287. doi:10.1182/bloodadvances.2016002493}

_{4. Fillmore NR, Yellapragada SV, Ifeorah C, et al. With equal access, African American patients have superior survival compared to white patients with multiple myeloma: a VA study. Blood. 2019;133(24):2615-2618. doi:10.1182/blood.2019000406}