The changing spectrum of infection with BCMA and GPRC5D targeting bispecific antibody (bsAb) therapy in patients with relapsed refractory multiple myeloma.

There is a paucity of granular data on infection risk with B-cell maturation antigen (BMCA) and GPRC5D bispecific antibodies (bsAb) in relapsed/refractory multiple myeloma (RRMM). The aim of our multi-institutional study was to characterize the incidence, etiologies, and risk factors of infections from the start of therapy to the last follow-up or 90 days after study exit. A total of 66 patients received BCMA bsAb monotherapy, 15 GPRC5D bsAb monotherapy, and 15 GPRC5D bsAb combination therapy with daratumumab and/or pomalidomide. While the infection rate per 100 days was 0.57 for BCMA bsAb, it was 0.62 for GPRC5D bsAb combination and 0.13 for GPRC5D bsAb monotherapy; P=0.05. The proportion of infections that were grade ≥3 was higher in the BCMA bsAb group compared to the GPRC5D groups (58% vs. 36%; P=0.04). Grade 5 events were observed in 8% (n=8) of the patients, all treated with BCMA bsAb. The 9 month cumulative incidence of any grade of infection was similar in the BCMA and GPRC5D-combination groups (57% and 62%) and significantly higher than in the GPRC5D-mono group (16%); P=0.012. The cumulative incidence of grade ≥3 infections was highest in the BCMA group reaching 54% at 18 months; P=0.06. Multivariate analysis showed that BCMA bsAb therapy or GPRC5D combination therapy, history of previous infections, baseline lymphopenia, and baseline hypogammaglobulinemia were significantly associated with a higher risk of grade ≥3 infections. Our results indicate that BCMA bsAb and GPRC5D-combination therapies in RRMM are associated with higher cumulative incidence of infection and grade ≥3 infection compared to GPRC5D bsAb mono.

Impact of postsurgical rehabilitation on outcomes for degenerative cervical myelopathy.

OBJECTIVE: Despite widespread use, there is limited evidence to support postsurgical rehabilitation to enhance neurological recovery after surgery for degenerative cervical myelopathy (DCM). Outcomes research for DCM seldom accounts for the effect of postsurgical rehabilitation. The aim of this study was to quantify the impact of postsurgical rehabilitation on outcomes after surgery for DCM. METHODS: This was a retrospective analysis of prospectively collected data from a single center. The study enrolled 66 patients who underwent spinal surgery for DCM. In addition to patient demographic, imaging, and surgical data, chart review was performed to document the timing, type, duration, and outcomes of postsurgical rehabilitation therapy. Outcomes were collected prospectively, including the modified Japanese Orthopaedic Association (mJOA) score, Neck Disability Index (NDI) score, and SF-36 physical component summary (PCS) score. Linear regression models were created to determine the independent effects of type and timing of postsurgical occupational therapy (OT) and physical therapy (PT) on outcomes. RESULTS: A total of 66 patients were included in the analysis. Multivariate regression analysis showed that postsurgical OT was associated with significantly greater improvement in 12-month SF-36 PCS scores (p = 0.009) and mJOA scores (p = 0.019). In the subset of patients who received therapy, delayed therapy (> 42 days after surgery) compared to early therapy (< 42 days after surgery) was associated with less improvement in SF-36 PCS scores (p = 0.03). CONCLUSIONS: Postsurgical outpatient rehabilitation was independently associated with improved postsurgical outcomes within the 1st year after surgery for DCM, and early therapy (< 42 days) was associated with superior outcomes compared to delayed therapy. This is one of the first studies to use a prospective database to demonstrate an independent effect for postsurgical rehabilitation on outcomes after surgery for DCM.

Autologous stem cell boost improves persistent immune effector cell associated hematotoxicity following BCMA directed chimeric antigen receptor T (CAR T) cell therapy in multiple myeloma.

Persistent Immune Effector Cell Associated Hematotoxicity (ICAHT) is a significant side effect of BCMA CAR T-Cell therapy in patients with relapsed multiple myeloma (MM). The use of stem cell boosts in ICAHT has been described, however studies have been limited by small patient numbers and short follow up. Herein, we report on our multi-institutional experience of ICAHT, defined by an absolute neutrophil count (ANC) of ≤ 1000, thrombocytopenia with a platelet count ≤ 50,000 or/and anemia as hemoglobin (hgb) ≤9 g/dL, in patients who received BCMA CAR T therapy, and the effects of subsequent stem cell boost on hematopoietic reconstitution and clinical outcome. In this study, ICAHT was observed in 60% (n = 61/101) of patients at D + 21, and risk factors for its development included history of a prior ASCT, higher number of prior lines of therapy, a decreased platelet count prior to lymphodepletion and history of ICANS. 28% of patients with ICAHT received a stem cell boost at a median of 116 days due to profound and prolonged cytopenias often requiring ongoing transfusion support. Stem cell boost significantly improved cytopenias at 3 and 6 months follow up without any adverse effects on PFS and OS, underscoring the safety of this procedure.