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81 24-Hour Urine Testing Does Not Add Value to Multiple Myeloma Response Assessments: A Secondary Analysis of BMT CTN 0702Clinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 653. Multiple Myeloma: Clinical and Epidemiological: Decluttering Responses and Dynamic Risk: How Can We Improve Prognostication in Multiple Myeloma?
Hematology Disease Topics & Pathways:
Research, Clinical trials, Clinical Practice (Health Services and Quality), Clinical Research, Health outcomes research, Plasma Cell Disorders, Diseases, Lymphoid Malignancies
Saturday, December 7, 2024: 10:00 AM

Rahul Banerjee, MD, FACP1,2, Amber R. Fritz, PhD3*, Othman S Akhtar, MD4, Ciara Louise Freeman, PhD, MSc, FRCPC, MRCP5, Andrew J. Cowan, MD2,6, Nina Shah, MD7,8, Heather J. Landau, MD9, Shaji Kumar, MD10, Dan T. Vogl, MD, MS11, Yvonne A. Efebera, MD12, Philip L. McCarthy, MD13, David H. Vesole, MD, PhD14, Adam Mendizabal, PhD3, Amrita Y Krishnan, MD, FACP15, George Somlo, MD16*, Edward A. Stadtmauer, MD17 and Marcelo C. Pasquini, MD, MS18

1University of Washington Fred Hutchinson Cancer Center, Seattle, WA
2University of Washington, Seattle, WA
3The Emmes Company, Rockville, MD
4Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
5Moffitt Cancer Center, Tampa, FL
6Fred Hutchinson Cancer Center, Seattle, WA
7AstraZeneca, South San Francisco, CA
8University of California San Francisco, San Francisco, CA
9Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
10Division of Hematology, Mayo Clinic, Rochester, MN
11Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA
12Blood and Marrow Transplant and Cellular Therapy Program, OhioHealth, Columbus, OH
13Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY
14Lombardi Comprehensive Cancer Center, Medstar Georgetown Medical Center, Washington, DC, DC
15City of Hope Comprehensive Cancer Center, Duarte, CA
16City of Hope Cancer Center, Duarte, CA
17Hospital of the University of Pennsylvania, Philadelphia, PA
18BMT and Cellular Therapy Program, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI

Background: 24-hour urine (24HRU) assessments are a key component of International Myeloma Working Group (IMWG) response criteria for multiple myeloma (MM) and are requested longitudinally in clinical trials even if not routinely used in real-world practice. Several analyses have suggested a limited role for 24HRU if serum immunofixation or free light chain (LC) testing is abnormal (Dejoie Blood 2016, Lahuerta Blood 2023). Adopting urine-free response criteria (with 24HRU removal from every level of IMWG response) may change responses in <5% of patients (Natsuhara et al, Leuk Lymph 2023) but not have been studied in terms of progression-free survival (PFS) in a larger population.

Methods: This was a secondary analysis of data from the Phase 3 BMT CTN 0702 (STaMINA) trial (Stadtmauer et al, JCO 2019) studying post-autologous stem cell transplantation (ASCT) strategies. Only patients evaluable for Day +56 response following ASCT were included, and patients with progressive disease (PD, n=8) at this timepoint were excluded. Post-ASCT responses relative to diagnosis were calculated by two sets of criteria. First, traditional responses were calculated per IMWG criteria (Kumar et al, Lancet Onc 2016) as stable disease (SD), partial response (PR), very good PR (VGPR), or complete response (CR, including stringent CR). Second, urine-free response assessments were calculated as follows: negative 24HRU immunofixation no longer required for CR, 24HRU M-protein < 100 milligrams (mg) per day no longer required for VGPR, and no 24HRU M-protein thresholds (e.g., < 200 mg per day or > 90% reduction) required for PR. PFS was estimated (using PD by traditional IMWG criteria or death as events) using proportional hazard models.

Results: Of 636 evaluable patients (84% of all BMT CTN 0702 participants), LC-only disease was noted in 18.9% (n=120). Pre-enrollment 24HRU testing at diagnosis was done in 28.9% of patients (n=184). IMWG responses were as follows: CR, 29.4% (n=187) traditional vs 29.7% (n=189) urine-free; VGPR, 37.0% (n=235) traditional vs 36.6% (n=233) urine-free; PR, 30.7% (n=195) for both; SD, 3.0% (n=19) for both. A total of 4 responses (0.6%) changed with urine-free criteria. Three patients were ‘upgraded’ (VGPR to CR, n=2, PR to VGPR, n=1) because 24HRU requirements for CR/VGPR were no longer required. One patient without a measurable serum paraprotein was ‘downgraded’ from a traditional VGPR (with negative 24HRU immunofixation) to a urine-free PR based on LC-only criteria. Among the subset of 184 patients with 24HRU electrophoresis results at diagnosis, there were no differences between traditional and urine-free IMWG responses.

Median PFS and 95% confidence intervals (CI) were the same at each depth of both traditional and urine-free criteria: 63.0 months (50.8 - 71.4 months) for CR, 49.6 months (42.6 - 55.1 months) for VGPR, 44.9 months (37.2-54.8 months) for PR, and 34.4 months (14.0-51.5 months) for SD. Urine-free IMWG criteria were highly prognostic for PFS (p = 0.006, 95% CI 1.05-1.36). The achievement of urine-free CR vs urine-free ≤CR was also prognostic (p = 0.005, 95% CI 0.54 - 0.89). Urine-free VGPR vs urine-free ≤VGPR was of borderline significance (p = 0.102, 95% CI 0.66 - 1.04), with median PFS 53.8 months (48.0 - 57.6 months) vs 44.6 months (36.3 - 54.7 months) respectively.

Discussion: In this secondary analysis of a Phase 3 trial, omitting 24HRU assessments from IMWG criteria changed <1% of responses and had no impact on PFS prediction at any response depth. 24HRU assessments had been performed for less than a third of patients as standard of care prior to study entry, underscoring its infrequent use outside of trials. Urine-free IMWG assessments would reduce time toxicity and discomfort for patients, particularly for those with limited dexterity. If implemented in trials, they would also simplify study logistics and lower operational costs. Outside of situations such as AL amyloidosis where 24HRU assessments remain critical or for patients with urine as their only measurable MM biomarker, our results support the removal of 24HRU assessments from future iterations of IMWG response criteria.

Funding: Grants #U10HL069294 and #U24HL138660 to the BMT CTN from the NHLBI and the NCI; contributions by Celgene Corporation and Millennium Pharmaceuticals, Inc.; funding by The Alliance for Clinical Trials in Oncology, the ECOG-ACRIN Cancer Research Group and SWOG.

Disclosures: Banerjee: Adaptive; BMS; Caribou Biosciences; Genentech; GSK; JNJ / Janssen; Karyopharm; Legend Biotech; Pfizer; Sanofi; SparkCures: Consultancy; Abbvie; JNJ; Novartis; Pack Health; Prothena; Sanofi: Research Funding. Fritz: Emmes Corporation: Current Employment. Akhtar: Sanofi: Honoraria. Freeman: Amgen: Consultancy; Incyte: Consultancy; ONK therapeutics: Consultancy; Janssen: Consultancy, Research Funding; Roche/Genentech: Research Funding; Sanofi: Consultancy; Abbvie: Consultancy; Celgene: Consultancy; Seattle Genetics: Consultancy; BMS: Consultancy, Honoraria, Research Funding. Cowan: Harpoon: Research Funding; Caelum: Research Funding; HopeAI: Consultancy, Current holder of stock options in a privately-held company; Sanofi: Consultancy, Research Funding; Regeneron: Research Funding; IgM biosciences: Research Funding; Nektar: Research Funding; Juno/Celgene: Research Funding; BMS: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy, Research Funding; Abbvie: Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Sebia: Consultancy. Shah: AstraZeneca: Current Employment, Current equity holder in publicly-traded company. Landau: Abbvie, Immix Biopharma, Legend Biotech, Alexion, Prothena: Consultancy; Nexcella, Janssen, Alexion, Protego, Prothena: Research Funding. Kumar: Merck: Research Funding; Roche: Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding; MedImmune/AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding; Oncopeptides: Other: Independent review committee participation. Vogl: Active Biotech: Research Funding; BMS: Consultancy; GlaxoSmithKline: Consultancy; Takeda: Consultancy, Research Funding; Abbvie: Consultancy; Genentech: Consultancy. Efebera: Takeda, Janssen, Akcea Therapeutics, Alnylum: Speakers Bureau; Oncopeptides, Sanofi, Janssen Oncology, Pfizer: Consultancy; Takeda, Oncopeptides, Alnylam, Sanofi, GlaxoSmithKline, ORCA Therapeutics, Bristol Myers Squibb/Celgene, Pharmacyclics through Alliance and AFT: Research Funding. McCarthy: BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees. Vesole: Amgen: Speakers Bureau; Takeda: Speakers Bureau; Karyopharm: Speakers Bureau; BMS: Speakers Bureau; Janssen: Speakers Bureau; Sanofi: Speakers Bureau. Mendizabal: Emmes Corporation: Current Employment. Krishnan: Bristol Myers Squibb: Current holder of stock options in a privately-held company; Johnson & Johnson: Membership on an entity's Board of Directors or advisory committees; City of Hope National Medical Center: Current Employment; AbbVie; Adaptive; Arcelx; GSK; Janssen; Roche; and Sanofi: Consultancy. Stadtmauer: Astra zeneca: Research Funding; Celgene, Takeda, Novartis, Teva, Janssen, Amgen, Sanofi: Consultancy. Pasquini: Bristol Myers Squibb: Consultancy, Research Funding; Novartis: Research Funding; Janssen: Research Funding; Kite, a Gilead Company: Honoraria, Research Funding.

*signifies non-member of ASH