(PA-247) Multiple Myeloma Patients with Admixture-defined African Ancestry Have Equal Clinical Outcomes to Those with European Ancestry When Receiving Highly Effective Therapies

Clinical outcomes in multiple myeloma (MM) patients according to race have been variably reported, with shorter progression-free survival (PFS) in Black patients in some cohorts, but equitable outcomes in other cohorts, particularly clinical trials. We recently participated in the Polyethnic-1000 initiative: using whole genome sequencing (WGS) to investigate cancers having a higher prevalence in Black populations. Here, we expand to a large cohort of clinically-available targeted sequencing data, considering topical regimens for newly-diagnosed and relapsed MM.  

Methods:

Data was assessed for all patients treated at MSKCC with daratumumab-based induction regimens (dara-quads), with a minimum of 3-month follow-up available. Genetic admixture was calculated from germline samples using the MSK-IMPACT-Heme targeted sequencing panel. Ancestry group was assigned by dominant contribution ( >50%) from 5 geographically-based populations (European; EUR, African; AFR, South Asian; SAS, East Asian; EAS, and Native American; NAM). Key somatic features and PFS were considered according to self-declared race and computed genetic admixture, using Fisher tests and Kaplan Meier respectively. As validation, PFS was also considered for patients receiving commercially-available CAR-T cells and bispecific antibodies (BsAb).

Results:

Clinical data was available from 506 patients treated with dara-quads, with self-declared data defining 74 Black, 349 White, 30 Asian and 53 Other / Unknown. Median age of diagnosis did not differ by race, being 63.7 years (y) for Black, 65.0y White, 64.2y Asian and 64.0y for Other. None of t(11;14), del17p/TP53mut or ISS III had a significantly different incidence by race. In addition, race did not predict for MRD-status after 4-6 cycles of induction, nor for PFS.

Admixture data from MSK-IMPACT-Heme was available for 286 patients treated with dara-quads, defining 215 EUR, 47 AFR, 11 SAS, 6 EAS, 1 NAM and 6 highly-admixed. 28 patients had self-declared “Other” or “Unknown” race, but with MSK-IMPACT-Heme data were able to be assigned to an ancestry group. 38 patients had admixture data available from both WGS and MSK-IMPACT-Heme and demonstrated 97% concordance. Restricting analysis to EUR and AFR due to available numbers, again, none of median age, incidence of t(11;14), del17p/TP53mut, ISS III, MRD-negativity nor PFS varied by ancestry group.

This data was confirmed in relapsed patients receiving CART (n=165) and BsAb (n=178), where again neither race nor genetic ancestry predicted for PFS.

Conclusions:

Clinical response to highly effective MM therapies in both induction and relapsed settings are equivalent when considering either self-declared race or computed genetic ancestry. Computed data allows inclusion of patients for whom race is unknown. Overall, this data suggests that any reported variance in clinical outcomes by race may largely indicate unequal healthcare access rather than biological difference in therapy-responsiveness.