CAR-T Therapy Versus Bispecific Antibodies in Relapsed Refractory Multiple Myeloma: Systematic Review and Metanalysis of Toxicity and Response

Introduction:

Relapsed refractory multiple myeloma (RRMM) remains a challenging clinical condition characterized by poor prognosis and limited effective treatment options. Emerging therapies such as CAR-T cell therapy and bispecific antibodies (BsAbs) have demonstrated encouraging outcomes; however, their clinical utility is guarded by toxicity profile. This systematic review and meta-analysis aims to compare the adverse event profile of CAR-T therapy and BsAbs in RRMM.

Methodology:

We identified 710 records from Medline, Embase, Web of Science, and Cochrane databases. Out of which, 33 studies were included in the final analysis. 24 studies evaluated CAR-T therapy (72.7%), 8 studies reported BsAbs (24.2%), and 1 study (3.1%) evaluated both the therapies. Primary outcome was expressed as pooled proportion and pooled incidence for adverse events and overall response rate (ORR) for efficacy with subgroup analysis performed where possible.

Results: The incidence of cytokine release syndrome (CRS) was 0.75 (95% CI [0.68;0.82]) in the entire cohort. The pooled incidence of CRS of any grade was 0.84 (95% CI [0.77,0.90]) amongst patients treated with CAR-T therapy, compared to 0.51 (95% CI [0.41, 0.61]) in those receiving BsAbs (p-value < 0.01). Mean time for resolution of CRS was 9.2 days in the entire cohort, with 9.8 days (95%CI [6.85, 12.75]) in CAR-T group versus 2.25 days (95% CI [2.06,2.44]) in the BsAbs group (p<0.01). No statistically significant difference was found in the timing of onset of CRS between the two groups. The incidence of Immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade was 0.27 (95% CI [0.08, 0.45]) in patients treated with CAR-T therapy, compared to 0.07 (95% CI [0.03, 0.10]) in those who received BsAbs (p=0.045). Pooled proportion of total infections was 0.36 (95% CI [0.27;0.45]) in CAR-T group compared to 0.31 (95% CI [0.11,0.51]) in the BsAbs group (p=0.67). Incidence of neutropenia was 0.89 (95% CI [0.83, 0.95]) with CAR-T therapy and 0.37 (95% CI [0.25, 0.48]) with BsAbs (p<0.01). Pooled incidence of thrombocytopenia with CAR-T was 0.70 (95% CI [0.57,0.84] and 0.31[0.15,0.47] with BsAbs (p<0.01). Similar statistically significant difference was seen with lymphopenia (CAR-T, 0.59[0.33,0.85]; BsAbs, 0.40 [0.26, 0.54). Incidence of minor side effects such as fatigue, headache, constipation, diarrhea, vomiting did not differ significantly between the two groups.

Pooled proportion of ORR was 0.84 (95% CI[0.77, 0.91]) in CAR-T group and 0.59 (95% CI[0.50, 0.67]) in BsAbs group(p< 0.01). The pooled proportion of mortality due to adverse events was 0.15 (95% CI[0.09, 0.20]) in CAR-T group and 0.14 (95% CI[0.06, 0.22]) in BsAbs group (p=0.94). The incidence of mortality due to multiple myeloma was 0.14 (95% CI [0.09, 0.19]). Subgroup analysis revealed insignificant difference between CAR-T; 0.15 (95% CI[0.10,0.21]) and BsAbs 0.08 (95% CI[0.02,0.14]) (p=0.07).

Conclusion: Bispecific antibodies demonstrated a more favorable toxicity profile compared to CAR-T therapy. However, CAR-T therapy was more efficacious than bispecific antibodies in terms of overall response rate. There was no difference between the two groups in terms of mortality rates attributable to either disease progression or adverse events.

Ramanathan:Spouse holds stocks in Boston scientific, Idxx, Medtronic, vertex, Sanofi, Novartis, Moderna, ISRG, Gilead, Dexcom, Alcon: Current holder of stock options in a privately-held company.