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. 2019 May 20;9(6):50.
doi: 10.1038/s41408-019-0209-5.

Patterns of survival in patients with recurrent mantle cell lymphoma in the modern era: progressive shortening in response duration and survival after each relapse

Anita Kumar  1 , Fushen Sha  2 , Ahmed Toure  2 , Ahmet Dogan  3 , Andy Ni  4 , Connie L Batlevi  2 , Maria Lia M Palomba  2 , Carol Portlock  2 , David J Straus  2 , Ariela Noy  2 , Steven M Horwitz  2 , Alison Moskowitz  2 , Paul Hamlin  2 , Craig H Moskowitz  2 , Matthew J Matasar  2 , Andrew D Zelenetz  2 , Anas Younes  2
Affiliations

Patterns of survival in patients with recurrent mantle cell lymphoma in the modern era: progressive shortening in response duration and survival after each relapse

Anita Kumar et al. Blood Cancer J. .

Abstract

As the survival of patients with mantle cell lymphoma (MCL) continues to improve, patients are increasingly being treated with multiple regimens. However, outcome after each line remains poorly characterized in the modern era. To address this knowledge gap, we retrospectively studied 404 consecutive MCL patients who were managed between 2000 and 2014 at Memorial Sloan Kettering Cancer Center. Histologic diagnosis was centrally confirmed, and patients were followed longitudinally from diagnosis throughout their disease course. Progression-free survival (PFS) and overall survival (OS) were determined by Kaplan-Meier method. The median OS and PFS after first-line treatment were 9.7 and 4.0 years, respectively. After second-line therapy, the median OS and PFS were 41.1 and 14.0 months, third line were 25.2 and 6.5 months, and fourth line were 14.4 and 5.0 months. In patients less than 65 years, stem cell transplant (SCT)-based frontline regimens were associated with improved PFS compared with non-SCT regimens (median PFS: 86.2 versus 40.0 months; P < 0.01), with a trend toward longer OS (median OS: 165.0 versus 120.0 months; P = 0.06). Early treatment failure after first-line regimens was associated with worse OS (5.9 versus 2.5 years; P < 0.01). Our study should facilitate establishing proper endpoints for future clinical trials using novel treatment approaches.

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Conflict of interest statement

A.K.: research funding from Abbvie Pharmaceuticals, Adaptive Biotechnologies, Celgene, Pharmacyclics, Seattle Genetics; advisory board member for Celgene (April 2016). F.S.: none. A.T.: none. A.D.: consultancy at Novartis, Weill-Cornell Hospital, Celgene, Seattle Genetics, Guidepoint Global Advisors, Pharmacyclics, Oncology Specialty Group, Roche, Peerview Institute, Physicians’ Education Resource, Corvus Pharmaceuticals. A.N.: none. C.L.B.: advisory for GLG, Defined Health; research funding from Novartis, Janssen, Bristol–Myers Squib, Epizyme, MedImmune; honoraria from Dava Oncology. M.L.M.P.: honoraria from Merck, Celgene and Pharmacyclics. C.P.: none. D.J.S.: consultancy at InPractice Elselvier, Seattle Genetics, Onco tracker (2016), Millenium (Takeda), DAVA (2016 and 2017), JUNO (2017), Bayer (2017); speaker’s bureau at ROCH China (2016), Medical Crossfire (2018). A.N.: research funding from Pharmacyclics, NIH, Raphael Pharma; consulting for: Janssen, Pharmacyclics, Medscape, Targeted Oncology. S.M.H.: consultancy at ADCT therapeutics, Aileron, Corvus, Forty-Seven, Innate Pharma, Kyowa-Hakka-Kirin, Millenium/Takeda, Mundipharma, Portola, Seattle Genetics; research funding from ADCT therapeutics, Aileron,Celgene, Forty-Seven, Infinity/Verastem, Kyowa-Hakka-Kirin, Millenium/Takeda, Seattle Genetics, Trillium. A.M.: consultancy at Kyowa Hakko Kirin Pharma, Miragen Therapeutics, Takeda Pharmaceuticals, ADC therapeutics, Seattle Genetics, Cell Medica, Bristol–Myers Squibb, Erytech Pharma; research funding from Incyte, Seattle Genetics, BMS, and Merck. P.H.: consultancy at Portola Pharmaceutics, Celgene, Karyopharm, Juno Therapeutics; research funding from Portola, Molecular Templates, Incyte, J&J Pharmaceuticals. C.H.M.: research funding from Merck, Seattle Genetics, BMS, ADC therapeutics Scientific Advisory Board: Novartis, Seattle Genetics, Takeda, Merck, BMS, Genentech, Astra Zeneca. M.J.M.: research funding from Genentech, Roche, GSK, Spectrum, Pharmacyclics, Seattle Genetics, Janssen; honoraria from Genentech, Roche, Spectrum, Janssen, Seattle Genetics, Rocket. A.D.Z.: consultancy at Genentech/Roche, Gilead, Celgene, Janssen, Amgen, Novartis, Adaptive Biotechnology; research funding MEI Pharma, MorphoSys, Sandoz, Celgene, Roche, Gilead; Board of Directors (DMC Chair) Beigene. A.Y.: research funding from Janssen, Novartis, Curis, Roche, BMS; honoraria or consulting fees from Bayer, Roche, BMS, Celgene, Incyte, Janssen, Curis, Takeda Millenium, Genentect, Merck, Xynomics, Bio-Path, and Epizyme.

Figures

Fig. 1
Fig. 1
Patient inclusion and treatment overview
Fig. 2
Fig. 2. Kaplan–Meier plots of overall survival (OS) since tumor diagnosis.
a OS for 404 patients since tumor diagnosis. b OS by initial observation or initial treatment after tumor diagnosis (p = 0.17)
Fig. 3
Fig. 3. Kaplan–Meier plots of overall survival (OS) and progression-free survival (PFS) in patients with mantle cell lymphoma treated with first-line therapy.
a, b OS and PFS for patients with or without upfront stem cell transplantation (SCT) as consolidation. c, d OS and PFS for patients older or younger than 65 years when first-line treatment was commenced. Patients older than 65 years had an inferior median OS (67.6 months; 95% CI, 57.1–85.0 months versus 158.5 months; 95% CI, 136.6–NR months; P < 0.01) and median PFS (32.3 months; 95% CI, 25.5–38.3 months versus 69.8 months; 95% CI, 56.8–91.5 months; P < 0.01). e, f OS and PFS for patients younger than 65 years when first-line treatment was commenced, with or without upfront SCT as consolidation. SCT was associated with a statistically significant difference in PFS (median PFS: 86.2 months; 95% CI, 65.4–147.0 months versus 40.0 months; 95% CI, 21.6–56.8 months; P < 0.01), and a trend towards improvement in OS (median OS: 165.0 months; 95% CI, 151.0–NR months versus 120.0 months; 95% CI, 101.0–NR months; P = 0.06)
Fig. 4
Fig. 4. Kaplan–Meier plots of overall survival (OS) and progression-free survival (PFS) in patients with mantle cell lymphoma treated with second-line therapy.
a, b OS and PFS for patients with early or late failure after first-line treatment. Patients who failed later to first-line treatment had superior median OS (70.4 months; 95% CI, 41.0–86.4 months versus 29.9 months; 95% CI, 26.4–41.1 months; P < 0.01) and median PFS (15.7 months; 95% CI, 13.4–21.0 months versus 9.7 months; 95% CI, 4.9–15.2 months; P < 0.01) when compared with patients who failed early. c, d OS and PFS for patients with or without blastoid/pleomorphic histology. Patients with blastoid or pleomorphic histology had inferior median OS (26.5 months; 95% CI, 10.9–31.4 months versus 70.8 months; 95% CI, 39.2–120.9 months; P < 0.01) and median PFS (5.4 months; 95% CI, 3.0–9.7 months versus 18.7 months; 95% CI, 15.1–40.9 months; P < 0.01). e, f OS and PFS for patients with or without stem cell transplantation (SCT) at second line. Patients with SCT consolidation in second remission had significantly better median OS (NR; 95% CI, 71.8-NR months versus 38.0 months; 95% CI, 28.8–44.2 months; P < 0.01) and median PFS (96.4 months; 95% CI, 29.6-NR months versus 10.9 months; 95% CI, 8.1–14.1 months; P < 0.01). g, h Among patients without SCT at second line, OS, and PFS by second-line treatment with or without ibrutinib. The addition of ibrutinib into salvage regimen was associated with improved median OS (NR; 95% CI, 42.4-NR months versus 31.1 months; 95% CI, 26.4–41.0 months; P = 0.02) and median PFS (23.3 months; 95% CI, 8.8–40.4 months versus 9.1 months; 95% CI, 6.6–13.4 months; P = 0.02)
Fig. 5
Fig. 5. Kaplan–Meier plots of overall survival (OS) and progression-free survival (PFS) in patients with mantle cell lymphoma after multiple lines of therapy.
a, b OS and PFS after treatment with line 1, line 2, line 3, line 4, and line 5–9
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