Introduction: T-cell redirecting therapies have demonstrated efficacy in patients (pts) with MM in the 4th line of treatment or later; however, pts with ultra-HRMM and plasma cell leukemia (PCL) were largely excluded from registrational trials. Here we report response data and survival outcomes for a cohort of ultra-HRMM/PCL pts who either received cellular therapies (CT), including bispecific antibodies (BSAb) or CAR-T, or conventional treatment regimens.
Methods: In this retrospective study, pts were required to have either PCL or at least two of the following cytogenetic abnormalities (CA) at the time of diagnosis: t(4;14), t(14;16), t(14;20), del(17p), del(1p32), and gain or amp 1q. Survival analysis was conducted using the Kaplan-Meier method with log-rank testing along with the Cox proportional hazards model for regression. 69 ultra-HRMM/PCL pts were identified. Of these, 30 pts received cellular therapies in the 4th line of therapy or later.
Results: The overall patient cohort had a median age of 62.1 years. Those receiving CT were more likely to have PCL and EMD as well as lower LDH and B2M at the time of diagnosis. The most common CA were gain/amp of 1q, del17p, and t(4;14). In the CT group, 100% and 73% of pts were triple and penta-refractory compared to 75% and 41% among those not receiving CT.
The median prior lines of therapy at the time of first treatment with CT was 7. 17 pts received CAR-T cells (8 Carvykti, 9 Abecma), 23 BSAb, and 10 pts multiple CT. ORR to first CT=40% (VGPR-10%, CR-23%), median DOR-6.5 mo.) MRD status was not available. CRS rate =82%, ICANS=35%, both of which were predominantly low grade. Overall, the median OS from 1st treatment was 51.8 months and 3-year OS was 61.0%. CT patients survived longer from 1st treatment: median OS=65.0 vs 32.2 mo. p=0.029. We then conducted a landmark 12-month OS analysis from the time of CT or last treatment for those note receiving CT. Overall the median OS was 6.3 months, 6-month OS was 51.8% and 12-month was 30.9%, however the survival curves exhibited a crossing hazards pattern with trends toward inferior survival for CT at one month and improved OS for CT at middle and later time (6-month OS: 63.9% with 95% CI 45.4-82.4 vs 45.6%, p= 0.16, 12-month OS: 40.7% vs 25.6, p = 0.18). Additional details of this analysis will be reported.
Conclusions: Within the limits of this analysis, a substantial minority of heavily pretreated pts with ultra-HRMM or PCL responded to late-line treatment with CT. When compared with patients who did not receive CT, landmark OS analysis conducted from the time of receipt of CT or last line of therapy suggests that early post-treatment mortality may offset some survival benefit in the intermediate term. Given the potential morbidity of these treatments, care should be taken in the selection of ultra-HRMM/PCL pts when considering late-line cellular therapies. The use of CT in earlier lines of therapy may allow for improvement of these outcomes and warrants further study in this vulnerable population.
