Key Takeaways
- Elranatamab Shows Promise in Relapsed or Refractory Multiple Myeloma (RRMM): The study evaluated the safety and efficacy of elranatamab—a bispecific antibody targeting BCMA—in patients with RRMM. Patients, both BCMA-naïve and -exposed, demonstrated improvements in patient-reported outcomes (PROs), particularly in pain reduction and disease symptom alleviation, suggesting elranatamab's potential as a treatment option for this challenging disease.
- Distinct PRO Profiles in BCMA-Naïve and BCMA-Exposed Patients: BCMA-naïve patients showed decreasing global health status scores initially but experienced improvements in pain reduction and disease symptom alleviation starting from cycle 4, persisting through cycle 12. BCMA-exposed patients had demonstrated stable baseline global health status scores but also experienced pain reduction and disease symptom alleviation, with a delayed onset compared to BCMA-naïve patients.
- Challenges and Limitations: While the study demonstrated favorable outcomes, challenges such as incomplete questionnaires and a decrease in population size over time posed limitations. These challenges underscore the need for stronger data collection methods and continuous patient follow-up to ensure comprehensive evaluation of treatment efficacy and PROs in RRMM patients receiving novel therapies.
Multiple myeloma (MM) is a disease without a cure that is characterized by severe symptoms that affect patient quality of life (QOL). B-cell maturation antigen (BCMA) is highly expressed on malignant plasma and serves as a promising selective immunotherapeutic target for the disease. A study published in British Journal of Haematology examined the patient-reported outcomes (PROs) from both BCMA-naïve and -exposed patients with relapsed or refractory (R/R) MM who were treated with elranatamab (Elrexfio; Pfizer), a bispecific antibody which targets BCMA on MM cells.
The trial, MagnetisMM-3 (NCT04649359), is an open-label, multicenter, non-randomized phase 2 study that evaluated the safety and efficacy of elranatamab monotherapy in patients with R/R MM. Enrolled patients were 18 years of age or older who were refractory to a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody, and were R/R to their most recent anti-MM regimen. Patients were divided into 2 cohorts depending on if they were not previously exposed to a BCMA-directed therapy such as an antibody-drug conjugate or chimeric antigen receptor (CAR)-T therapy and were considered BCMA-naïve (cohort A), or if they were BCMA-exposed (cohort B).
All patients received step-up doses of elranatamab, which was administered subcutaneously (12 mg on day 1 and 32 mg on day 4), followed by the full treatment dose of 76 mg weekly beginning on day 8. Dose cycles were 28 days in length and doses could be modified if necessary, depending on elranatamab-related toxicities or peripheral neuropathy. Further, for both step-up and full doses, premedication that consisted of 650 mg of acetaminophen (or 500 mg of paracetamol), 25 mg of diphenhydramine, and 20 mg of dexamethasone was administered an hour prior to the elranatamab dose.
PROs were the exploratory end points of the study, with measures being administered electronically on days 1 and 15 during the first 3 cycles, and on day 1 of each subsequent cycle through cycle 12. In addition, cancer-specific global health status and QOL, functioning, and symptoms were collected using myeloma-specific questionnaires. For example, the QLQ-C30 cancer-specific questionnaire was used in this analysis, and gathers data across 5 functional scales (physical, role, cognitive, emotional, and social), 1 global health status scale, 3 symptom scales (pain, fatigue, and either nausea or vomiting), and 6 single items (dyspnea, insomnia, loss of appetite, constipation, diarrhea, and financial difficulties). Better health was indicated by higher scores on the 5 functional scales and the global health scale, whereas higher scores on the symptom scare demonstrated a greater degree of symptom severity. In addition, other scales were used to assess health status across 5 domains (mobility, self-care, usual activities, pain, and anxiety or depression) and the overall sense of a change in disease state since beginning treatment.
According to the analysis, 123 BCMA-naïve and 64 BCMA-exposed patients were enrolled in the study and had a median follow-up of 14.7 months after the final patient’s initial dose. The investigators noted differences between the 2 cohorts, particularly the incidence of extramedullary disease and the median number of prior lines of therapy, which were both greater in BCMA-exposed patients (57.8% and 7.5 lines of therapy) than in BCMA-naïve patients (31.7% and 5.0 lines of therapy). In addition, the authors note that most patients in both cohorts had triple-class refractory disease, with 42.3% and 51.6% of cohort A and cohort B, respectively, also having penta-drug refractory disease. Further, patients who were exposed to BCMA had underwent BCMA-directed ADC (71.9%), CAR-T cell therapy (32.8%), or both (4.7%); however, the majority (57.8%) were refractory to these therapies.
The QLQ-30 questionnaire indicated that BCMA-naïve patients had worsening in their mean global health status scores compared to baseline (LSM change [95% CI], −5.9 [−10.7 to −1.1]), followed by an improvement back to baseline levels on the first day of cycle 3 that remained consistent until the first day of cycle 12. Further, cohort A had significant reductions in pain beginning on the first day of cycle 4 (−6.7 [−13.0 to −0.4]) and was maintained until the start of cycle 12. Reductions in pain were present by day 15 of the third cycle and continued through the beginning of cycle 5 for cohort B.
In addition, the MM-specific questionnaire demonstrated that patients who were BCMA-naïve had significant reductions in their disease symptoms during cycle 5 (−6.9 [−10.6 to −3.1]) and were maintained through cycle 12. These patients had also experienced a worsening in side effects of the disease, which was initially observed during the end of cycle 2 (4.3 [1.4–7.2]). Further, side effect scores for BCMA-exposed patients remained at baseline level until day 1 of cycle 9, improved during cycle 10, and were back to baseline levels at the start of cycle 11. For both cohorts, significant improvements in future perspective domain scores that were observed as early as day 15 of the first cycle (5.2 [1.1–9.2] and 5.8 [0.9–10.8] respectively), and these scores had either continued to improve or were maintained through day 1 of cycle 12.
According to the investigators, the main limitation of the study was incomplete questionnaires, which was due to patient death, treatment discontinuation, or lack of follow-up. In addition, the authors noted that the population size in each cohort had decreased slightly over time, resulting in some missing values.
Reference
Mohty M, Bahlis NJ, Nooka AK, DiBonaventura M, Ren J, Conte U. Impact of elranatamab on quality of life: Patient-reported outcomes from MagnetisMM-3. Br J Haematol. 2024; 00: 1–10. doi:10.1111/bjh.19346
