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2417 Is Tandem ASCT Needed in MM Patients with High Risk Cytogenetics in the Era of Maintenance Therapy? Results from the Canadian Myeloma Research Group (CMRG) Database

Program: Oral and Poster Abstracts
Session: 731. Clinical Autologous Transplantation: Results: Poster II
Hematology Disease Topics & Pathways:
multiple myeloma, Diseases, Non-Biological, Therapies, chemotherapy, Plasma Cell Disorders, Lymphoid Malignancies
Sunday, December 6, 2020, 7:00 AM-3:30 PM

Peter Duggan, MD, FRCPC1, Donna E. Reece, MD2, Kevin Song, MD3, Victor Jimenez-Zepeda, MD1, Arleigh McCurdy, MD, BSc4, Martha L Louzada, MD, MSc5, Hira S Mian, MD6, Michael Sebag, MD, PhD7, Darrell J White, MD8, Julie Stakiw, MD9, Richard Leblanc, MD, FRCPC10, Esther Masih-Khan2*, Eshetu G Atenafu, M.Sc., P.Stat11*, Rami Kotb, MD12*, Muhammad Aslam, MD13*, Anthony Reiman, MD14*, Engin Gul, BS, MBA15* and Christopher P. Venner, MD16

1Tom Baker Cancer Center, Department of Hematology, University of Calgary, Calgary, AB, Canada
2Princess Margaret Cancer Centre, Toronto, ON, Canada
3BC Cancer Agency, The University of British Columbia, Vancouver, BC, Canada
4Department of Medicine, Division of Hematology, The Ottawa Hospital, Ottawa, ON, Canada
5London Health Sciences Centre, London, ON, Canada
6Department of Oncology, McMaster University, Hamilton, ON, Canada
7Division of Hematology, McGill University Health Centre, Montreal, QC, Canada
8Nova Scotia Health Authority, Halifax, NS, Canada
9Saskatoon Cancer Centre, Saskatoon, SK, Canada
10Hôpital Maisonneuve-Rosemont, Université de Montréal, Montreal, QC, Canada
11Princess Margaret Cancer Centre, Department of Biostatistics, University Health Network, University of Toronto, Toronto, ON, Canada
12Cancer Care Manitoba, Winnipeg, MB, Canada
13Allan Blair Cancer Center, Regina, SK, Canada
14University of New Brunswick, Saint John Regional Hospital, Saint John, NB, CAN
15University Health Network-PMH, Vaughan, ON, Canada
16Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada

Background: Recent studies evaluating tandem autologous transplantation for multiple myeloma (MM) show conflicting results in terms of efficacy. However subgroup analysis suggests that those with high-risk disease may benefit the most from tandem transplant. We used the CMRG database to compare single versus tandem ASCT for patients with MM with high-risk cytogenetics.

Methods: The primary objective was to compare PFS in MM patients with high-risk cytogenetics (p53 deletion, t(4;14), t(14;16)) identified from the CMRG database undergoing front-line single or tandem ASCT from 01/2010 to 06/2019. Secondary objectives compared OS, ORR, and outcomes based on whether post-transplant maintenance was given. OS and PFS rates were calculated from the date of first ASCT using the Kaplan-Meier method. ORR was assessed by Chi-square using best response post ASCT.

Results: There were 302 single and 125 tandem transplants, followed by maintenance therapy in 190 (63%) and 96 (77%) respectively. Translocation (4;14) was seen in 209 (49%), t(14:16) in 61 (15.6%) and delP53 in 222 (52%) with more than one abnormality in 65 patients. The most common induction regimen consisted of cyclophosphamide, bortezomib, and steroids, (83%) followed by bortezomib and dexamethasone (8%) and dexamethasone alone (4.7%). Forty-seven patients (11%) required reinduction prior to first ASCT with regimens including RVD (49%), Rd (23%) and others (D/DT/VD-PACE, CyBor-D, KRD, VD, IxaRD, 28%). Maintenance was prescribed to 286 patients with regimens including lenalidomide ± dexamethasone (65%), lenalidomide + proteasome inhibitor ± dexamethasone (22%), proteasome inhibitor ± dexamethasone (11%) and others (2%). Patient characteristics are summarised in table 1.

The overall response rate was 93.9% (94.5% for single ASCT and 92% for tandem ASCT). The PFS at 3 years was 41.1% (single) and 45.7% (tandem) with median PFS 26 vs 35 months respectively (p=0.0621). Three year OS was 71.5% (single) and 83.8% (tandem), median OS 83 vs 89 months (p=0.0060).

Both PFS and OS were improved with the use of maintenance therapy, regardless of single vs tandem transplant. PFS at 3 years was 52.1% for those receiving maintenance therapy compared to 21.7% for no maintenance (median 42 vs 16 months, p<0.0001). Overall survival was 79.5% with maintenance vs 63.6% without (median 92 vs 60 months, p<0.0001). Figures 1 shows PFS and OS for single or tandem transplant, with or without maintenance therapy. There was no difference in PFS or OS after a single or tandem transplant when maintenance was given. PFS for single or tandem ASCT with maintenance at 3 years was 53.7% and 46.3% respectively (p=0.527). Three year OS rates were 76.7% and 85.6% (p=0.0962). However, PFS was better with tandem compared to single ASCT when no maintenance was given. PFS at 3 years for single transplant with no maintenance was 19.0% (median 13 months) vs 48.9% (median 23.7 months) for tandem without maintenance (p=0.0084), while OS were not statistically different (62.4% vs 74.7%, median 60 months vs not reached, p=0.5271).

Conclusions: Tandem ASCT does improve outcomes for MM with high-risk cytogenetics. However, the main benefit was seen in patients who did not receive maintenance therapy. Our data demonstrate the potent anti-myeloma effect of post-ASCT maintenance and raise the question of the optimal role of tandem ASCT in the modern treatment era.

Disclosures: Duggan: Novartis: Honoraria; Amgen: Consultancy; Celgene: Consultancy; Astra Zeneca: Consultancy; Jannsen: Consultancy. Reece: Janssen, Bristol-Myers Squibb, Amgen, Takeda: Consultancy, Honoraria; Janssen, Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Research Funding; Otsuka: Research Funding. Song: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen, Celgene,Takeda: Consultancy, Honoraria; Otsuka: Honoraria. Jimenez-Zepeda: Janssen, Celgene, Amgen, Takeda: Honoraria. McCurdy: Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Sanofi: Honoraria; GSK: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Louzada: Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Mian: Takeda: Consultancy, Honoraria; Celgene: Consultancy; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Sanofi: Consultancy. Sebag: Celgene: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria, Research Funding. White: Takeda: Honoraria; Sanofi: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Karyopharm: Honoraria; Antengene: Honoraria; GSK: Honoraria. Stakiw: Lundbeck: Honoraria; Celgene: Honoraria; BMS: Honoraria; Roche: Research Funding; Janssen: Honoraria, Research Funding; Amgen: Honoraria; Novartis: Honoraria. Leblanc: Celgene Canada; Janssen Inc.; Amgen Canada; Takeda Canada: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding. Kotb: Takeda: Honoraria; Sanofi: Research Funding; Janssen: Honoraria; Amgen: Honoraria; Celgene: Honoraria; Karyopharm: Current equity holder in publicly-traded company; Merck: Honoraria, Research Funding. Venner: Janssen, BMS/Celgene, Sanofi, Takeda, Amgen: Honoraria; Celgene, Amgen: Research Funding.

*signifies non-member of ASH