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3363 Gain1q in Myeloma Randomized Clinical Trials- How Is It Reported and How Does It Impact Outcomes: A Systematic Review

Program: Oral and Poster Abstracts
Session: 652. Multiple Myeloma: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
clinical trials, Research, Clinical Research, Therapies
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Karun Neupane, MD, MBBS1, Gliceida Galarza Fortuna, MD2*, Riyasha Dahal, MBBS3*, Timothy M Schmidt, MD4, Rafael Fonseca, MD5, Doug Sborov6, Meera Mohan, MD7, Hira Mian, MD8, Rajshekhar Chakraborty, MD9 and Ghulam Rehman Mohyuddin, MD10

1Jacobi Medical Center/Albert Einstein College of Medicine, Bronx, NY
2Department of Internal Medicine, University of Utah, Salt Lake City, UT
3Universal College of Medical Sciences, Bhairahawa, Nepal
4University of Wisconsin School of Medicine and Public Health, Madison, WI
5Mayo Clinic, Phoenix, AZ
6University of Utah School of Medicine, Salt Lake City, UT
7BMT and Cellular Therapy Program, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
8Juravinski Cancer Center, Hamilton, ON, Canada
9Columbia University Medical Center, New York, NY
10Huntsman Cancer Institute, University of Utah, Salt Lake City, UT


Extra copies of chromosome 1q21 (+1q: gain=3 copies, amp=4 or more copies) have been associated with worse outcomes for patients with multiple myeloma (MM). We performed a systematic review to evaluate current reporting of +1q, efficacy of existing regimens for +1q, and prognostic implications of +1q in MM randomized controlled trials (RCTs).


We searched three databases for MM RCTs. Our inclusion criteria were all published MM RCTs from 2012-2022. Each MM RCT was analyzed for reported data on +1q. The following features specific to +1q were collected: +1q reported or not as a high-risk cytogenetic alteration, definition of gain1q with respect to percentage of cells with abnormality detected, documentation of distinction between Gain1q and Amp1q in analysis, prevalence of +1q in enrolled population, outcomes of patients [Overall Survival (OS) and Progression Free Survival (PFS)] in patients with +1q in the experimental versus control arm and in patients with and without +1q.


A total of 124 trials were included. Among these trials, 28 (23%) studies reported data on +1q, including 26 studies that reported data in the primary manuscript and two studies that reported in separate publication. These trials reported a total of 2692 patients with +1q which represented 25% of all the patients enrolled. Out of 28 trials, three trials (11%) specified the criteria for categorizing patients as +1q (example in IKEMA and IFM-99: the presence of at least three copies in at least 30% of analyzed plasma cells was required). Only four trials (14%) reported survival data on gain and amp separately and the remaining 24 (86%) studies reported for gain or did not specify gain vs amp. Amongst the trials that reported +1q, 22 (79%) considered this to be a high-risk cytogenetic abnormality.

Amongst trials that met primary endpoint showing improvement in PFS and clearly reported on +1q, the following drugs also improved PFS for those with +1q (when comparing hazard ratio (HR) for intervention versus control arm in the +1q subgroup): lenalidomide (len) maintenance in Myeloma XI, selinexor in BOSTON, and isatuximab in IKEMA and ICARIA.

Several trials met their endpoint and showed improvement in PFS in the +1q cohort in same direction as overall study results but had confidence intervals for +1q subgroup that crossed 1. These included addition of carfilzomib in Myeloma XI, addition of carfilzomib vs bortezomib to len and dex for +1q (but not in Amp1q) in ENDURANCE, addition of elotuzumab to pomalidomide and dex, and bortezomib-based treatment before and after autologous stem cell transplantation (auto-SCT) vs no bortezomib (Table 2).

Seven studies reported HR for patients with +1q in the trial (across both arms) compared to those without. In six studies (all studies other than SWOG1211), worse outcomes were seen with respect to OS and PFS for those with +1q versus without (Table 2).

Important interventions for which subgroup analysis of +1q was not presented in trial results, and hence conclusions about the efficacy of the drugs specifically for patients with +1q cannot be ascertained included pomalidomide and ixazomib. Although subgroup analysis of various daratumumab trials has shown improvement for high-risk MM, the effect on gain1q was not isolated. Two recent contemporary trials that isolated effect of auto-SCT (DETERMINATION and IFM-2009) did not report +1q. However, in FORTE Trial, adverse prognostic implications of +1q were not seen in the arm receiving carfilzomib, len, dex and auto-SCT, indicating a possible role of carfilzomib and auto-SCT in ameliorating the adverse prognostic implications of +1q. Although len maintenance improved PFS after auto-SCT as maintenance in Myeloma XI overall for those with +1q, it did not appear to improve PFS for patients with isolated +1q (with no other concurrent genetic abnormalities).


This systematic review of MM RCTs finds considerable heterogeneity in the reporting of +1q abnormalities in the literature, and +1q to be inconsistently classified as a poor prognostic factor in subgroup analysis of randomized myeloma trials. Most interventions that have shown to be successful in randomized trials and have clearly reported on the +1q subgroup have shown concordant direction of results and benefit of the applied intervention in the +1q subgroup. A more standardized approach to reporting of this abnormality is needed.

Disclosures: Fonseca: FISH: Patents & Royalties: FISH; Millenium: Consultancy; Caris Life Sciences: Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy; AZBio: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; Merck: Consultancy; Janssen: Consultancy; Bayer: Consultancy; Binding Site: Consultancy; Antegene: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy; BMS (Celgene): Consultancy; Sanofi: Consultancy; Regeneron: Consultancy; Pharmacyclics: Consultancy; Juno: Consultancy; Aztrazenica: Consultancy; Oncotracker: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; AMGEN: Consultancy; Adaptive Biotechnologies: Consultancy; AbbVie: Consultancy. Sborov: Abbvie: Consultancy; BMS: Consultancy; Pfizer: Consultancy, Research Funding; Bioline: Consultancy, Research Funding; Arcellx: Consultancy, Research Funding; Gilead: Research Funding; Amgen: Research Funding; Cantex: Research Funding; Sanofi: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; GSK: Consultancy, Research Funding; RocheX: Research Funding. Mohan: GlaxoSmithKline plc: Research Funding; MJH life sciences: Honoraria; Institutional KL2 Award: Other: Research Grant; Sanofi S.A: Consultancy, Research Funding; Takeda Pharmaceutical Company: Research Funding; Ionis Pharmaceuticals: Research Funding; Bristol-Myers Squibb Company: Research Funding; Celgene Corporation: Research Funding; Novartis: Research Funding; Amgen Inc: Research Funding; Blood Cancer Today: Honoraria; MashupMD: Honoraria; Bristol myers squibb/Celgene: Consultancy; Pfizer: Consultancy. Mian: GSK Awards: HHS Research Early Career Award from Hamilton Health Sciences Foundation: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Celgene: Honoraria; Janssen: Honoraria. Chakraborty: Adaptive Biotechnologies: Consultancy; Sanofi Pasteur: Consultancy; Janssen: Consultancy.

*signifies non-member of ASH