Outcomes of urgent inpatient chemotherapy for relapsed/refractory multiple myeloma in the modern era Free

Introduction: Patients (pts) with relapsed/refractory (R/R) multiple myeloma (MM) often receive urgent chemotherapy (chemo) in the inpatient (inpt) setting for disease progression (PD). The long-term benefits and outcomes of such interventions remain undefined. We report a retrospective study evaluating outcomes of urgent inpatient chemo for R/R MM.

Methods: The analysis includes 82 adult pts (≥18 years) with R/R MM who received unplanned inpt chemo at the Cleveland Clinic from January 2021 to October 2023. Pts receiving planned chemo were excluded. Pt and disease characteristics were analyzed. Primary endpoints assessed include inpt chemo continuation at 3 months post discharge, response rates, 3-month overall survival (OS) and progression-free survival (PFS) rates, and 30-day mortality after inpt chemo. OS and PFS were estimated using the Kaplan-Meier method, and the log-rank test was used for comparisons in univariate analysis (UVA).

Results: The median age at the time of admission was 61.5 years (range 44–86). A majority of the pts were female (56%), Caucasian (72%), and had poor performance status, with an ECOG ≥2 (52%). Most pts (95%) had MM, while 5% had plasma cell leukemia. At the time of initial diagnosis, the Revised International Staging System stage was II-III in 45% of the pts. Charlson comorbidity scores on admission were 0-2 in 39%, 3-4 in 37%, and ≥5 in 23%. Lytic bone lesions and extramedullary disease were present in 96% and 37% of pts respectively. Renal dysfunction (glomerular filtration rate (GFR) < 45 mL/min/1.73m²) and anemia (Hb < 8.5 g/dL) were present in 48% each. Hypoalbuminemia [<4 gm/dl], thrombocytopenia (<100 k/µL), and elevated lactate dehydrogenase [LDH] (>225 U/L) were noted in 87%, 57%, and 52% of pts, respectively. The median number of prior therapies was 4 (range 1-15). Refractory disease to the last line of therapy was observed in 66% of pts, and 44% had relapsed after a prior autologous transplant.

Among the inpt chemo regimens used, VTD-PACE (bortezomib, thalidomide, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, and etoposide) was the most common regimen (42%), followed by daratumumab-based (27%), bortezomib-based (16%), and others (24%). The median hospital stay was 10 days (range 2–89). A subset of pts required a higher level of care: intensive care unit (ICU) stay (29%), use of vasopressors (20%), mechanical ventilation (13%), and dialysis (21%). The median days of ICU stay was 6 (range 2-83).

More than half (55%) received growth factors post chemo. Most pts were discharged home (68%), 17% were discharged to a rehab facility, and 6% transitioned to hospice. The 30-day readmission, ED visit, and ICU admission rates were 37%, 38%, and 35%, respectively. Post-chemo complications include cytopenias (61%) and infections (34%). Less than half (43%) continued the inpatient chemo regimen post-discharge, with only 7 pts remaining on the same regimen for 3 months. Moreover, the response rates were poor, with 24 pts experiencing PD, 21 partial responses, and 8 very good partial responses, with only 2 complete remissions. A subset of pts received novel therapies like bispecific (22%) and CAR T-cell therapy (21%) for relapsed disease after admission.

The median OS was 4.9 months (95% CI: 3.4-9.4), and the median PFS was 1.5 months (95% CI: 1.2-2.6). The 3-month PFS and OS rates were 38% (95% CI: 28-50%) and 68% (95% CI: 59-79%), respectively. At the time of analysis, 88% of the cohort were dead, with only 10% alive without PD. MM was the leading cause of death (57%). The 30-day mortality rate after inpt chemo was 16%. On UVA, pts refractory to the last line of therapy (p_OS = .0035; p_PFS = .0363) and those requiring ICU admission (p_OS = 0.0012; p_PFS = 0.0156) had inferior OS and PFS. Discharge to home was associated with better survival (p_OS = 0.0021; p_PFS = 0.0344). High LDH (p=.0384) and low GFR (≤40-60 mL/min/1.73m²) (p=.0234) predicted worse OS. Treatment with bispecifics (p = 0.0005) and CAR-T (p = 0.0121) following inpt chemo was associated with improved OS; however, it had no significant impact on PFS.

Conclusions: Urgent inpt chemo for RR MM resulted in dismal outcomes with median OS <6 months. Refractoriness to last therapy, ICU stay, high LDH, discharge home, and use of novel therapies were key determinants for survival. Although the rapid emergence of novel therapies for MM broadens treatment options, careful patient selection remains critical to optimize outcomes.