Early Relapse After Autologous Stem Cell Transplantation in Multiple Myeloma is Still Prognostic in The Era of Novel Agents

Semih Başcı, Tuğçe Nur Yiğenoğlu, Bahar Uncu Ulu, Mehmet Bakırtaş, Derya Şahin, Tahir Darçın, Jale Yıldız, Alparslan Merdin, Nuran Ahu Baysal, Dicle İskender, Merih Kızıl Çakar, Mehmet Sinan Dal, Tuba Hacıbekiroğlu, Fevzi Altuntaş


Significant improvements in the prognosis of Multiple Myeloma(MM) have recently observed in the era of novel agents. Induction treatment, including new agents followed by conditioning regimen and upfront autologous stem cell transplantation(ASCT), has been accepted as the standard treatment approach for newly diagnosed eligible MM patients. Despite novel agents, upfront ASCT is still superior to conventional chemotherapy alone. Previous studies revealed that the duration between ASCT and relapse had predicted overall survival(OS), and meantime, it was widely used to determine the potential benefit from a second ASCT. However, the majority of the data collected reflects the treatment modalities before novel agents. In this study, we aimed to investigate the impact of post-transplantation early relapse(ER) on survival in the era of novel agents. The results of 155 MM patients that underwent ASCT at our center between January 2010 and May 2018 were analyzed retrospectively. The median follow-up duration was 20 months in the ER group, 27 months in the non-ER group, and 24 months in all patients. 33.3% of patients in the ER group and 71.4% of patients in the non-ER group were alive at the time of analysis. Median OS was 20.77±3.66 months in the ER group and 40.89±4.21 months in the non-ER group. We found a statistically significant relationship between the ER and the poor OS (p:<0.001). Our study reveals that in the era of novel agents, ER still related to poor survival. Therefore, comprehensive studies needed to develop new strategies for early relapsed patients.


Multiple myeloma; autologous stem cell transplantation; early relapse

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Attal, M., Lauwers-Cances, V., Hulin, C., Leleu, X., Caillot, D., Escoffre, M., Arnulf, B., Macro, M., Belhadj, K., Garderet, L., Roussel, M., Payen, C., Mathiot, C., Fermand, J. P., Meuleman, N., Rollet, S., Maglio, M. E., Zeytoonjian, A. A., Weller, E. A., Munshi, N., … IFM 2009 Study (2017). Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma. The New England journal of medicine, 376(14), 1311–1320. https://doi.org/10.1056/NEJMoa1611750

Brenner, H., Gondos, A., & Pulte, D. (2008). Recent major improvement in long-term survival of younger patients with multiple myeloma. Blood, 111(5), 2521–2526. https://doi.org/10.1182/blood-2007-08-104984

Corradini, P., Cavo, M., Lokhorst, H., Martinelli, G., Terragna, C., Majolino, I., … Gahrton, G. (2003). Molecular remission after myeloablative allogeneic stem cell transplantation predicts a better relapse-free survival in patients with multiple myeloma. Blood, 102(5), 1927–1929. https://doi.org/10.1182/blood-2003-01-0189

Durie, B. G. M., Harousseau, J. L., Miguel, J. S., Bladé, J., Barlogie, B., Anderson, K., … Morgan, G. (2006). International uniform response criteria for multiple myeloma. Leukemia, 20(9), 1467–1473. https://doi.org/10.1038/sj.leu.2404284

Gay, F., Oliva, S., Petrucci, M. T., Conticello, C., Catalano, L., Corradini, P., … Palumbo, A. (2015). Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: A randomised, multicentre, phase 3 trial. The Lancet Oncology, 16(16), 1617–1629. https://doi.org/10.1016/S1470-2045(15)00389-7

Gay, F., Oliva, S., Petrucci, M. T., Montefusco, V., Conticello, C., Musto, P., … Boccadoro, M. (2017). Autologous transplant vs. oral chemotherapy and lenalidomide in newly diagnosed young myeloma patients: A pooled analysis. Leukemia, 31(8), 1727–1734. https://doi.org/10.1038/leu.2016.381

Harousseau, J.-L. (2008). Autologous transplantation for multiple myeloma. Annals of Oncology, 19, 128–133. https://doi.org/10.1093/annonc/mdn449

Jimenez-Zepeda, V. H., Reece, D. E., Trudel, S., Chen, C., Tiedemann, R., & Kukreti, V. (2015). Early relapse after single auto-SCT for multiple myeloma is a major predictor of survival in the era of novel agents. Bone Marrow Transplantation, 50(2), 204–208. https://doi.org/10.1038/bmt.2014.237

Kastritis, E., Zervas, K., Symeonidis, A., Terpos, E., Delimbassi, S., Anagnostopoulos, N., … Dimopoulos, M. A. (2009). Improved survival of patients with multiple myeloma after the introduction of novel agents and the applicability of the International Staging System (ISS): An analysis of the Greek Myeloma Study Group (GMSG). Leukemia, 23(6), 1152–1157. https://doi.org/10.1038/leu.2008.402

Kumar, S. K., Rajkumar, S. V., Dispenzieri, A., Lacy, M. Q., Hayman, S. R., Buadi, F. K., … Gertz, M. A. (2008). Improved survival in multiple myeloma and the impact of novel therapies. Blood, 111(5), 2516–2520. https://doi.org/10.1182/blood-2007-10-116129

Kumar, S., Mahmood, S. T., Lacy, M. Q., Dispenzieri, A., Hayman, S. R., Buadi, F. K., … Gertz, M. A. (2008). Impact of early relapse after auto-SCT for multiple myeloma. Bone Marrow Transplantation, 42(6), 413–420. https://doi.org/10.1038/bmt.2008.180

Lee, H., Duggan, P., Chaudhry, A., Neri, P., Tay, J., Rashid-Kolvear, F., … Jimenez-Zepeda, V. H. (2018). Early Relapse for Multiple Myeloma Patients Undergoing Single Autologous Stem Cell Therapy: A Single-center Experience. Clinical Lymphoma, Myeloma, and Leukemia, 18(1), e69–e75. https://doi.org/10.1016/j.clml.2017.10.009

Martinelli, G., Terragna, C., Zamagni, E., Ronconi, S., Tosi, P., Lemoli, R. M., … Cavo, M. (2000). Molecular remission after allogeneic or autologous transplantation of hematopoietic stem cells for multiple myeloma. Journal of Clinical Oncology, 18(11), 2273–2281. https://doi.org/10.1200/JCO.2000.18.11.2273

Majithia, N., Rajkumar, S. V., Lacy, M. Q., Buadi, F. K., Dispenzieri, A., Gertz, M. A., … Kumar, S. K. (2016). Early relapse following initial therapy for multiple myeloma predicts poor outcomes in the era of novel agents. Leukemia, 30(11), 2208–2213. https://doi.org/10.1038/leu.2016.147

Michaelis, L. C., Saad, A., Zhong, X., Le-Rademacher, J., Freytes, C. O., Marks, D. I., … Hari, P. (2013). Salvage Second Hematopoietic Cell Transplantation in Myeloma. Biology of Blood and Marrow Transplantation, 19(5), 760–766. https://doi.org/10.1016/j.bbmt.2013.01.004

Mikhael, J., Ismaila, N., Cheung, M. C., Costello, C., Dhodapkar, M. V., Kumar, S., … Martin, T. (2019, May 10). Treatment of multiple myeloma: ASCO and CCO joint clinical practice guideline. Journal of Clinical Oncology, (37), pp. 1228–1263. https://doi.org/10.1200/JCO.18.02096

Ong, S. Y., De Mel, S., Chen, Y. X., Ooi, M. G., Surendran, S., Lin, A., … Gopalakrishnan, S. K. (2016). Early relapse post autologous transplant is a stronger predictor of survival compared with pretreatment patient factors in the novel agent era: Analysis of the Singapore Multiple Myeloma Working Group. Bone Marrow Transplantation, 51(7), 933–937. https://doi.org/10.1038/bmt.2016.43

Palumbo, A., Cavallo, F., Gay, F., Di Raimondo, F., Yehuda, D. B., Petrucci, M. T., … Cavo, M. (2014). Autologous transplantation and maintenance therapy in multiple myeloma. New England Journal of Medicine, 371(10), 895–905. https://doi.org/10.1056/NEJMoa1402888

Palumbo, A., Bringhen, S., Falco, P., Cavallo, F., Ambrosini, M. T., Avonto, I., … Boccadoro, M. (2007). Time to first disease progression, but not β2-microglobulin, predicts outcome in myeloma patients who receive thalidomide as salvage therapy. Cancer, 110(4), 824–829. https://doi.org/10.1002/cncr.22855

Palumbo, A., & Cavallo, F. (2012, December 6). Have drug combinations supplanted stem cell transplantation in myeloma? Blood, (120), pp. 4692–4698. https://doi.org/10.1182/blood-2012-05-423202

Rihn, C., Cilley, J., Naik, P., Pedicano, A. V. J. & Mehta, J. (2004). Definition of myeloid engraftment after allogeneic hematopoietic stem cell transplantation. Haematologica, 89(6), 763–764. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/15194552

Szalat, R., & Munshi, N. C. (2019, January 1). Novel agents in multiple myeloma. Cancer Journal (United States), (25), pp. 45–53. https://doi.org/10.1097/PPO.0000000000000355

Venner, C. P., Connors, J. M., Sutherland, H. J., Shepherd, J. D., Hamata, L., Mourad, Y. A., … Song, K. W. (2011). Novel agents improve survival of transplant patients with multiple myeloma, including those with high-risk disease defined by early relapse (<12 months). Leukemia and Lymphoma, 52(1), 34–41. https://doi.org/10.3109/10428194.2010.531409


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