Prognostic Factors for Survival in Multiple Myeloma Patients That Receive Bispecific Antibodies: Does Relative Dose Intensity Matters?

Background

Relative Dose Intensity (RDI) affects the outcomes of several neoplasms, including Multiple Myeloma (MM). However, due to the mechanism of action of Bispecific Antibodies (BsAbs), RDI may not necessarily be as relevant. Our objective is to describe clinical characteristics, prognostic factors and survival impact of RDI in a cohort of MM patients treated with BsAbs.

Materials and Methods

MM Patients treated in a single institution with BsAbs between oct/2021 and apr/2024 were included. Demographic, treatment and outcomes characteristics were collected with REDCap®. RDI was estimated based on the Prescribing Information for each BsAb, and calculated multiplying by 100 the total amount of dose received over the total expected dose during the treatment time [PMID: 30696949] without an expected number of cycles. Day 1 of treatment was the day of first given dose, and last day of treatment was the day of last dose given when treatment was interrupted due to dose-limiting toxicity, progression or death. Progression Free Survival (PFS), defined from the time from first dose of BsAb until progression of disease (based on IMWG criteria) or death, and Overall Survival (OS), were analyzed.

Results

40 MM patients treated with BsAbs were identified. Median age at diagnosis was 61.9 years (IQR=15) and median age at time of BsAbs administration was 71.5 years (IQR=14.5). 65% of patients were female. Most patients were Non-Hispanic White (NHW, 60%) followed by Non-Hispanic Blacks (10%) and Hispanics (5%). ECOG <2 was seen in 67.5%. 50% were ISS stage II. High-Risk Cytogenetic Abnormalities (HRCA) were seen in 42.5%. Median follow up since diagnosis was 117.8 months, and since starting the BsAbs was 12 months. Median of lines of treatments prior to BsAbs were 7 (IQR=6) and 65% of cases were Triple-Class Refractory.

Elranatamab was received by 42.5%, followed by Teclistamab (40%) and Talquetamab (17.5%). 45% of patients reached complete response with the BsAbs. Median PFS was 8.9 months (CI95%=0.0-18.5) and median OS was not reached, with 3-year OS of 60%.

Median RDI was 93.4% (IQR=33.2). Median duration of treatment was 99.5 days (IQR=245). The median time to loss the 100% compliance with treatment was 42 days (IQR=65.2). 87.5% of patients with low RDI (<95%) had a treatment duration ≥100 days, meanwhile 89.5% of patients with high RDI (≥95%) had a duration of treatment of <100 days (p<0.001).

RDI ≥95% was seen in patients with high CAR-HEMATOTOX score compared to low (77.8% vs 23.1%, p=0.011), early (≤1 month) vs late onset (>1 month) of neutropenia (87.5% vs 12.5%, p<0.001) and in patients without severe neutropenia compared with those with severe neutropenia (75.0% vs 16.7%, p=0.009). No difference in RDI was seen by gender, race, ISS stage or BsAb.

The most frequent reasons for any treatment interruption (70% each) were CRS/ICANS, neurotoxicity, renal failure, liver toxicity and osteomuscular problems. Treatment was stopped due to progression of disease in 35% of cases, followed by toxicity in 35.2%. 17.5% of cases received another different BsAbs after our analyzed first course of treatment.

Median PFS for patients with RDI ≥95% was 1.1 months (CI95%=0.15-2.01) vs the PFS for RDI<95% was 27.1 months (CI95%=9.48-44.66), p=0.003. Multivariate Cox regression for PFS showed that RDI ≥95% is an independent prognostic factor for survival (HR=18.1, p<0.01). Also, worse PFS is associated with female gender (HR=17.6, p<0.01), ECOG ≥2 (HR=16.2, p<0.01), ISS stage III (HR=8.8, p=0.02), HRCA (HR=7.6, p<0.01), linfopenia prior to BsAbs (HR 8.0, p=0.03) and teclistamab compared with elranatamab (HR=6.3, p=0.01). Better prognosis was seen for Hispanic when compared to NIW (HR=0.008, p<0.01). no significant effect of age at time of administration of BsAbs was observed.

Conclusions

In this retrospective cohort, achieving a high RDI was associated with worse PFS, and does not seem to be essential in BsAb, potentially due to the longstanding therapeutic effect of BsAb even after holding the medication. Lower RDI benefit seems to be driven by longstanding responders that receive treatment with less RDI due to dose-limiting toxicity or preference, meanwhile a high compliance (RDI 100%) is more frequently seen in patients with early relapse. This is translated in improved PFS in this cohort. Impact of RDI on outcomes can help guide treatment length in immunotherapy.