Cohen, Inbar

ABSTRACT Oligo‐secretory and non‐secretory MM present a clinical challenge due to the difficulties in initial diagnosis, response to treatment assessment, and relapse detection. They are excluded from most clinical trials, which typically require measurable disease. We describe the characteristics and outcomes of 86 patients with secretory myeloma at diagnosis who developed an OSR, matched 1:1 to a cohort with secretory relapse (SR). With a median follow‐up of 9.3 years, 16.6% (48/289) of evaluable patients developed an OSR. Lower levels of light chains at presentation, and younger age are predictive of an OSR. The median OS since relapse of the OSR group was 4.01 (95% CI 1.625–6.395) versus 3.25 (95% CI 2.255–4.245) years in the SR control group ( p = 0.4). A third of our OSR cohort had a subsequent SR. We did not find any predictive factor for SR after OSR. The median OS of the subgroup of patients who developed a SR after OSR was 3.35 years (95% CI 1.541–5.159), versus 5.8 years (95% CI 2.072–9.528) in the group that remained oligo‐secretory ( p = 0.336). The median TTNT of the SR after OSR group was 1.68 years (95% CI 0.341–0.919) versus 4.58 (95% CI not reached‐not reached) in the group that remained oligo‐secretory ( p < 0.001).

Background In 2014, the IMWG updated the criteria for diagnosing multiple myeloma (MM) and added three additional criteria to the traditional CRAB criteria. The new criteria called the SLiM criteria, include clonal bone marrow plasma cells ≥60%, involved to uninvolved free light chain ratio (rFLC) ≥100 (involved FLC must be ≥ 100 mg/L), and &gt; one focal lesion on MRI studies (each lesion ≥ 5 mm). These criteria were deemed myeloma-defining events (MDE) in the absence of CRAB criteria. Autologous stem cell transplantation (ASCT) has been used for treating MM for over three decades and is safe and efficacious. We report on outcomes of outpatient ASCT in a cohort of patients with MM where therapy was initiated solely based on SLiM criteria. Methods We conducted a retrospective study of all patients diagnosed with MM based on SLiM criteria at Mayo Clinic, Rochester, MN. We compared this cohort to a matched cohort of newly diagnosed MM patients whose MDE was CRAB and who underwent an ASCT. For every patient whose MDE was SLiM, we matched two patients whose MDE was CRAB. The matching was done by age, gender, and melphalan dose. Results Between 2013 and 2022, 30 patients received an ASCT due to SLiM criteria at Mayo Clinic, Rochester (Durie Salmon Stage IA). The median age of our cohort was 63 (range 46-75) years, and 60% had an ISS of 1. Seventeen percent of the cohort was treated with DVRd induction. The median time from diagnosis to ASCT was 6.5 months (IQR 6-7), and all but one received full intensity conditioning with melphalan 200 mg/m2. 53% of patients completed the ASCT without requiring hospitalization, and 47% (n=14) of patients required hospitalization with a median duration of hospital admission of 6 days (IQR 5-14). Bacteremia was confirmed in 7 patients (23%). The matched cohort included 60 patients. Baseline characteristics were similar, with the exception of lower hemoglobin levels in the control group, as expected (13.1 vs 12, P=0.0017). No differences were seen in the number of cells collected (3.4 vs 3.67 X106 cells/kg, P=0.19) or the use of Plerixafor (80% vs 78%, P=0.8). The SLiM cohort had a shorter median time to neutrophil (15 vs 16 days, P=0.049) and platelet (15 vs 17 days, P=0.0004) engraftment. Similar hospitalization and bacteremia rates were seen. The overall response rate was 100%, with a complete response or better (sCR/CR) seen in 30% of patients. The matched cohort had an ORR of 98%, with sCR/CR of 37%. The MRD- rate was the same in both groups. More patients in the SLiM cohort achieved VGPR (50%) than in the CRAB cohort (27%). None of the patients died within 100 days of transplant. The 36-month OS was 100% in the SLiM group and 93.3% in the control group (95% CI 83.1%-97.4%), with a trend towards higher OS in the SLiM cohort (P=0.065). The 36-month PFS was 91.61% in the SLiM cohort (95% CI 69.93-97.87%) and 65.95% in the control group (95% CI 52.31%-76.53%). There was no difference in the PFS between the cohorts (P=0.414). Conclusion ASCT is efficacious and safe in MM patients transplanted only due to SLIM criteria. Improved MRD- and longer PFS were not seen despite lower ISS stage disease in the SLiM group.

Summary In 2014, the International Myeloma Working Group (IMWG) updated the criteria for diagnosing myeloma and added three additional criteria to the traditional Calcium elevation, Renal impairment, Anemia, Bone disease (CRAB) criteria, called the Sixty % marrow plama cells, Light chain ratio >60, Mri demonstates lytic lesions (SLiM) criteria (clonal bone marrow plasma cells ≥60%, involved to uninvolved free light chain ratio (FLCr) ≥100 and >1 focal lesion on magnetic resonance imaging (MRI)). We report on the outcomes of 30 patients who underwent autologous stem cell transplantation (ASCT) where therapy was initiated solely based on SLiM criteria and compared them to a matched cohort of 60 patients whose myeloma‐defining event was CRAB. The SLiM cohort had a shorter median time to neutrophil (15 vs. 16 days, p = 0.049) and platelet (15 vs. 17 days, p = 0.0004) engraftment. The 36‐month overall survival (OS) was 100% in the SLiM group and 93.27% in the control group (95% CI 83.06%–97.42%), with a trend towards longer OS in the SLiM cohort ( p = 0.065). The 36‐month progression‐free survival (PFS) was 91.61% in the SLiM (95% CI 69.93%–97.87%) and 65.95% in the control group (95% CI 52.31%–76.53%). There was no difference in the PFS between the cohorts ( p = 0.414). ASCT is efficacious and safe in MM patients transplanted only due to SLIM criteria. Early intervention in this asymptomatic cohort did not appear to result in deeper responses or better PFS compared to outcomes in symptomatic patients.