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Letters to the Editor
favored the use of LM. The disease control and survival advantage of LM persisted in patients with standard- or high-risk cytogenetics. Interestingly, patients with high- risk cytogenetics treated with LM had superior PFS and OS compared with standard-risk patients in the non-LM cohort, a finding that supports using LM even in patients anticipated to have the poorer survival outcomes associ- ated with these cytogenetic abnormalities. Lastly, the improved PFS2 outcomes in LM patients demonstrates that non-LM patients do not “catch up” to their mainte- nance counterparts with second-line therapy.
LM further improved survival outcomes in each response category, including those in the nCR/CR group. This suggests that the impact of LM on PFS and OS goes beyond simply improving patients’ response criteria and offers additional survival advantages even in those who achieve a nCR/CR, perhaps through an immune as well as a cytotoxic effect.
Although most patients required a dose reduction or medication discontinuation at some point during their treatment, only 19.6% of patients discontinued therapy prior to relapse. This suggests that LM is well-tolerated.
Limitations of our study include its retrospective, observational nature. Patients were enrolled who started chemotherapy prior to 2016 and significant changes have emerged in the field of myeloma in recent years, particu- larly with regards to novel chemotherapeutic agents in the setting of relapsed disease. These may have influ- enced the OS data which depends in part on treatment received for disease recurrence. Given that the non-LM cohort largely comprises of those starting chemotherapy prior to 2012, these patients may not have had the same access to clinical trials or novel combination therapy as their LM counterparts. On the other hand, patients pro- gressing on LM might be expected to experience poorer results with second-line therapy, which was not the case based on PFS2 data. However, the similarity of our data when compared to large scale, randomized, controlled trials suggests that the impact of this temporal relation- ship between the LM and non-LM groups may not signif- icantly impact our results. Further, the availability of additional agents only affects the PFS2 and OS outcomes. The cohort presented here is still reflective of the impact of LM on disease control in the post-ASCT setting as measured by PFS.
Lastly, the recent adoption of LM limits our ability to see its full impact on survival outcomes as many of LM patients have not yet experienced their first relapse. Longer follow-up will allow further assessment of the impact of maintenance therapy, particularly in the era of improved therapy for relapsed disease.
Despite the limitations of retrospective data, large mul- ticenter datasets have undeniable merits as they allow for evaluation of the generalizability of new treatments in patients who would not meet eligibility criteria for a clin- ical trial. Such datasets also provide lengthy and detailed follow-up of real-world data beyond the line of treatment in question, which can be challenging to collect in prospective randomized control trials.2,5,9-11 Furthermore, those with early relapse as well as long-term disease-free survivors are easily identified in these large, retrospective datasets. Examination of their data will be useful in the determination of contributing and prognosticating factors in these, and other, patient subsets.
In summary, our retrospective cohort validates the data seen in large phase 3 trials demonstrating the positive impact LM has had on PFS, OS and response in the real- world setting. This data supports the ongoing use of LM as a current standard of care.
Hannah M. Cherniawsky,1 Vishal Kukreti,2 Donna Reece,2 Esther Masih-Khan,2,3 Arleigh McCurdy,4
Victor H. Jimenez-Zepeda,5 Michael Sebag,6 Kevin Song,7 Darrell White,8 Julie Stakiw,9 Richard LeBlanc,10
Anthony Reiman,11 Muhammad Aslam,12 Martha Louzada,13 Rami Kotb,14 Engin Gul,3 Eshetu Atenafu3
and Christopher P. Venner15
1University of Alberta, Edmonton, Alberta; 2Medical Oncology and Hematology, Princess Margaret Cancer Center, Toronto, Ontario; 3Canadian Myeloma Research Group, Toronto, Ontario; 4The Ottawa Hospital, Ottawa, Ontario; 5Tom Baker Cancer Center, Calgary, Alberta; 6Department of Oncology, Division of Hematology, McGill University, Montreal, Quebec; 7BC Cancer, Vancouver General Hospital, Vancouver, British Columbia; 8Queen Elizabeth II Health Sciences Center, Dalhousie University, Halifax, Nova Scotia; 9Saskatoon Cancer Center, University of Saskatchewan, Saskatoon, Saskatchewan; 10Maisonneuve- Rosemont Hospital Research Center, University of Montreal, Montreal, Quebec; 11Department of Oncology, Saint John Regional Hospital, Saint John, New Brunswick; 12Allan Blair Cancer Center, Regina, Saskatchewan; 13London Regional Cancer Center, London, Ontario; 14Cancer Care Manitoba, Winnipeg, Manitoba and 15Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada
Correspondence:
ESTHER MASIH-KHAN - esther.masih-khan@uhnresearch.ca doi:10.3324/haematol.2020.259093
Received: June 15, 2020.
Accepted: September 30, 2020.
Pre-published: October 13, 2020.
Disclosures: VK received honoraria from Amgen, Takeda and Celgene; DC received research funding from Otsuka, Celgene, Janssen, Takeda, Merck, BMS, and Millennium, acts as a consultant for Celgene, Jansen, Amgen, Karyopharm and Takeda, and received honoraria from Celgene, Janssen, Amgen and Takeda; AmcC received honoraria and acts as a consultant for Celgene, Janssen, Amgen, Takeda; JVHJ-Z received honoraria from Celgene, Janssen, Takeda, Merck and BMS; MS is a member on an entity's Board of Directors or advisory committees of Janssen Inc., Amgen, Takeda, Celgene; KS received research funding from Celgene., honoraria from Celgene, Janssen, Amgen and Takeda; DW received honoraria from Amgen, Antengene, Celgene, Janssen, Karyopharm, Sanofi and Takeda; RLB is a member on an entity's Board of Directors or advisory committees of Celgene Canada, Janssen Inc., Amgen, Takeda, Sanofi and received research funding from Celgene (co-investigator); ML received honoraria from Janssen, Celgene, Amgen, Pfizer; CPV received honoraria from Janssen, Amgen, Takeda and research funding Celgene Amgen; all remaining authors declare non conflicts of interest.
Contributions: HMC, CPV, VK, DR, and EMK designed research, performed research, collected, analyzed, interpreted data and wrote the manuscript. EA performed statistical analysis, analyzed, interpreted data and wrote the manuscript; All authors designed research, analyzed and interpreted data.
Acknowledgments: the authors would like to thank the Canadian Myeloma Research Group for their support and our patients for generously donating their data for analysis.
References
1. Attal M, Harousseau JL, Stoppa AM, Sotto JJ, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome. N Engl J Med. 1996;335(2):91-97.
2. McCarthy PL, Holstein SA, Petrucci MT, et al. Lenalidomide mainte- nance after autologous stem-cell transplantation in newly diagnosed multiple myeloma: a meta-analysis. J Clin Oncol. 2017;35(29):3279- 3289.
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