Session: 652. Multiple Myeloma and Plasma Cell Dyscrasias: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Clinical Research, Plasma Cell Disorders, Diseases, Lymphoid Malignancies
METHODS: We performed a single-center retrospective analysis on patients that were seen at the University of California San Francisco Hematology clinic for MIDD from 2010 to 2020. All pts must have had biopsy-proven R-MIDD. Demographic and disease-related characteristics at diagnosis were collected as well therapies administered. Diagnosis of multiple myeloma was per IMWG criteria (Rajkumar et al. Lancet Oncology 2014). Hematologic response and renal response were assessed per previously published criteria (Palladini et al. J Clin Oncol 2012; Palladini et al. Blood 2014). Overall survival (OS), time-to-next treatment (TTNT), time-to-renal progression (TTRP), time-to-dialysis (TTD) were estimated using the Kaplan-Meier method. TTRP was defined as time from the start of treatment to renal progression censored by last follow-up or date of renal transplant. TTD was defined as time from start of treatment to dialysis or last follow-up. Pts already on dialysis at diagnosis were excluded from TTRP and TTD.
RESULTS: Thirty-four pts with R-MIDD were identified, 31 light chain deposition disease, 2 heavy chain deposition disease and 1 light and heavy chain deposition disease. Median age at diagnosis was 63 (IQR 58-70) with 13 (38.2%) females. Median creatinine and estimated GFR at diagnosis were 2.80 mg/dL (IQR 3.17-5.57) and 25 ml/min/1.73m2 (IQR 13-40) respectively. Median involved free light chain (FLC) was 819 mg/L (IQR 130-2870), and difference in FLC 433 mg/L (IQR 85-1022). All pts had abnormal serum free light chains and 25 (73.5%) pts had kappa R-MIDD. Median bone marrow plasma cells percentage was 19% (IQR 10-38%). The most common cytogenetic abnormality was del 13 in 6/25 pts (24.0%). A concurrent diagnosis of myeloma was presented in 10 (32.3%) pts.
Pts underwent a median of 2 lines of treatment (IQR 1-2). Median follow-up was 5.95 years (range 0.27 - 22.3 years). Pts were treated at induction with the following therapies: Group 1) immunomodulatory drug (IMiD) +/- bortezomib (Bor) (8/34, 23.5%); Group 2) Bor without IMiD (24/34, 70.6%) or Group 3) other (2/34, 5.9%). Autologous stem cell transplant (ASCT) was performed in 82.4% of pts. The 3- and 6-month hematologic response of ≥VGPR was 30.4% (7/23) and 55.6% (15/27) respectively. At the 6-month, Group 1, 2 and 3 had a ≥VGPR of 14.3%, 26.3% and 100% respectively though Group 3 only had 2 pts. Of the 29 pts assessed for best renal response, 9 pts (31.0%) had a renal response. Best renal response for group 1, 2, and 3 occurred in 0%, 38.1% and 100% of pts, respectively. Median TTNT was 2.9 years.
Of 34 pts, only 5 died and median overall survival was not reached (Fig.1A). Improved median OS was associated with diagnosis after 2010 v ≤2010 (p=0.1) (Fig. 1B), >60 years old at diagnosis v ≤60 (p=0.1) (Fig. 1C) and treatment with ASCT (p=0.058) (Fig. 1D), though none met statistical significance.
Renal progression occurred in 63.3% pts with median TTRP of 1.8 years. Dialysis dependence occurred in 33.3% pts with median TTD not reached (Fig. 2A). TTD did not differ significantly for pts diagnosed >2010 v ≤2010 (p=0.9) (Fig. 2B), ASCT (p=0.7) (Fig. 2D) though was better for pts who were diagnosed >age 60 vs ≤60 (p=0.027) (Fig. 2C). Five pts had a renal allograft, 3 of whom received the allograft after chemotherapy initiation, with 1 graft failure.
In a landmark analysis at 6 months, OS and TTRP was better in pts with ≥VGPR compared to <VGPR, though both did not meet statistical significance (p=0.3 and p=0.2, respectively) (data not shown). No significant difference between ≥VGPR compared <VGPR was observed in TTD (p=0.5) (data not shown).
CONCLUSION: In this limited retrospective study, we showed that R-MIDD pts were diagnosed late in the disease when pts already developed severe CKD. R-MIDD pts frequently had a concomitant diagnosis of multiple myeloma. Despite treatment with novel agents and ASCT, only a third of pts had a renal response and a third of pts required eventual dialysis. This study highlights the need for early diagnosis of R-MIDD and better treatments for this disease.
Disclosures: Chung: Janssen: Research Funding; Cellectis: Research Funding; AbbVie: Research Funding; Caelum: Research Funding; Merck: Research Funding; BMS/Celgene: Research Funding; Sanofi: Honoraria. Wolf: Adaptive Biotechnologies: Consultancy. Martin: Legend Biotech: Consultancy; GlaxoSmithKline and Legend Biotech: Consultancy; Amgen, Johnson & Johnson / Janssen, Sanofi, and Seattle Genetics: Research Funding. Shah: GSK, Amgen, Indapta Therapeutics, Sanofi, CareDx, Kite, Karyopharm, Oncopeptides,: Consultancy; Aztra Zeneca: Current Employment, Other: stock ownership; AstraZeneca: Current Employment, Current equity holder in publicly-traded company; Celgene/BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar, Precision Biosciences: Research Funding. Wong: Bristol Myers Squibb: Research Funding; Dren Bioscience: Consultancy; Sanofi: Membership on an entity's Board of Directors or advisory committees; Fortis: Research Funding; Genentech: Research Funding; Patient Discovery: Research Funding; Caelum: Research Funding; Janssen: Research Funding; GSK: Research Funding; Catalent Biologics: Consultancy.
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