Second primary malignancies with lenalidomide therapy for newly diagnosed myeloma: a meta-analysis of individual patient data

Antonio Palumbo, Sara Bringhen, Shaji K Kumar, Giulia Lupparelli, Saad Zafar Usmani, Anders Waage, Alessandra T Larocca, Bronno R Van Der Holt, Pellegrino Musto, Massimo Offidani, Maria Teresa Petrucci, Andrea Evangelista, Sonja Zweegman, Ajay K Nooka, Andrew Spencer, Meletios Athanasios Dimopoulos, Roman Hajek, Michele M Cavo, Paul G Richardson, Sagar Lonial & 6 others Giovannino Ciccone, Mario Boccadoro, Kenneth Carl Anderson, Bart M Barlogie, Pieter Sonneveld, Philip L McCarthy

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: Lenalidomide has been linked to second primary malignancies in myeloma. We aimed to pool and analyse available data to compare the incidence of second primary malignancies in patients with and without lenalidomide exposure. Methods: We identified relevant studies through a search of PubMed and abstracts from the American Society of Clinical Oncology, American Society of Hematology, and the International Myeloma Workshop. Randomised, controlled, phase 3 trials that recruited patients with newly diagnosed multiple myeloma between Jan 1, 2000, and Dec 15, 2012, and in which at least one group received lenalidomide were eligible for inclusion. We obtained individual patient data (age, sex, date of diagnosis, allocated treatment and received treatment, duration of treatment and cause of discontinuation, maintenance treatment, date of first relapse, date of second primary malignancy diagnosis, type of second primary malignancy, date of death or last contact, and cause of death) by direct collaboration with the principal investigators of eligible trials. Primary outcomes of interest were cumulative incidence of all second primary malignancies, solid second primary malignancies, and haematological second primary malignancies, and were analysed by a one-step meta-analysis. Findings: We found nine eligible trials, of which seven had available data for 3254 patients. 3218 of these patients received treatment (2620 had received lenalidomide and 598 had not), and were included in our analyses. Cumulative incidences of all second primary malignancies at 5 years were 6?9 (95 CI 5?3-8?5) in patients who received lenalidomide and 4?8 (2?0-7?6) in those who did not (hazard ratio [HR] 1?55 [95 CI 1?03-2?34]; p=0?037). Cumulative 5-year incidences of solid second primary malignancies were 3?8 (95 CI 2?7-4?9) in patients who received lenalidomide and 3?4 (1?6-5?2) in those that did not (HR 1?1 [95 CI 0?62-2?00]; p=0?72), and of haematological second primary malignancies were 3?1 (95 CI 1?9-4?3) and 1?4 (0?0-3?6), respectively (HR 3?8 [95 CI 1?15-12?62]; p=0?029). Exposure to lenalidomide plus oral melphalan significantly increased haematological second primary malignancy risk versus melphalan alone (HR 4?86 [95 CI 2?79-8?46]; p
Original languageEnglish
Pages (from-to)333 - 342
Number of pages10
JournalLancet Oncology
Volume15
Issue number3
DOIs
Publication statusPublished - 2014

Cite this

Palumbo, A., Bringhen, S., Kumar, S. K., Lupparelli, G., Usmani, S. Z., Waage, A., ... McCarthy, P. L. (2014). Second primary malignancies with lenalidomide therapy for newly diagnosed myeloma: a meta-analysis of individual patient data. Lancet Oncology, 15(3), 333 - 342. https://doi.org/10.1016/S1470-2045(13)70609-0
Palumbo, Antonio ; Bringhen, Sara ; Kumar, Shaji K ; Lupparelli, Giulia ; Usmani, Saad Zafar ; Waage, Anders ; Larocca, Alessandra T ; Van Der Holt, Bronno R ; Musto, Pellegrino ; Offidani, Massimo ; Petrucci, Maria Teresa ; Evangelista, Andrea ; Zweegman, Sonja ; Nooka, Ajay K ; Spencer, Andrew ; Dimopoulos, Meletios Athanasios ; Hajek, Roman ; Cavo, Michele M ; Richardson, Paul G ; Lonial, Sagar ; Ciccone, Giovannino ; Boccadoro, Mario ; Anderson, Kenneth Carl ; Barlogie, Bart M ; Sonneveld, Pieter ; McCarthy, Philip L. / Second primary malignancies with lenalidomide therapy for newly diagnosed myeloma: a meta-analysis of individual patient data. In: Lancet Oncology. 2014 ; Vol. 15, No. 3. pp. 333 - 342.
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title = "Second primary malignancies with lenalidomide therapy for newly diagnosed myeloma: a meta-analysis of individual patient data",
abstract = "Background: Lenalidomide has been linked to second primary malignancies in myeloma. We aimed to pool and analyse available data to compare the incidence of second primary malignancies in patients with and without lenalidomide exposure. Methods: We identified relevant studies through a search of PubMed and abstracts from the American Society of Clinical Oncology, American Society of Hematology, and the International Myeloma Workshop. Randomised, controlled, phase 3 trials that recruited patients with newly diagnosed multiple myeloma between Jan 1, 2000, and Dec 15, 2012, and in which at least one group received lenalidomide were eligible for inclusion. We obtained individual patient data (age, sex, date of diagnosis, allocated treatment and received treatment, duration of treatment and cause of discontinuation, maintenance treatment, date of first relapse, date of second primary malignancy diagnosis, type of second primary malignancy, date of death or last contact, and cause of death) by direct collaboration with the principal investigators of eligible trials. Primary outcomes of interest were cumulative incidence of all second primary malignancies, solid second primary malignancies, and haematological second primary malignancies, and were analysed by a one-step meta-analysis. Findings: We found nine eligible trials, of which seven had available data for 3254 patients. 3218 of these patients received treatment (2620 had received lenalidomide and 598 had not), and were included in our analyses. Cumulative incidences of all second primary malignancies at 5 years were 6?9 (95 CI 5?3-8?5) in patients who received lenalidomide and 4?8 (2?0-7?6) in those who did not (hazard ratio [HR] 1?55 [95 CI 1?03-2?34]; p=0?037). Cumulative 5-year incidences of solid second primary malignancies were 3?8 (95 CI 2?7-4?9) in patients who received lenalidomide and 3?4 (1?6-5?2) in those that did not (HR 1?1 [95 CI 0?62-2?00]; p=0?72), and of haematological second primary malignancies were 3?1 (95 CI 1?9-4?3) and 1?4 (0?0-3?6), respectively (HR 3?8 [95 CI 1?15-12?62]; p=0?029). Exposure to lenalidomide plus oral melphalan significantly increased haematological second primary malignancy risk versus melphalan alone (HR 4?86 [95 CI 2?79-8?46]; p",
author = "Antonio Palumbo and Sara Bringhen and Kumar, {Shaji K} and Giulia Lupparelli and Usmani, {Saad Zafar} and Anders Waage and Larocca, {Alessandra T} and {Van Der Holt}, {Bronno R} and Pellegrino Musto and Massimo Offidani and Petrucci, {Maria Teresa} and Andrea Evangelista and Sonja Zweegman and Nooka, {Ajay K} and Andrew Spencer and Dimopoulos, {Meletios Athanasios} and Roman Hajek and Cavo, {Michele M} and Richardson, {Paul G} and Sagar Lonial and Giovannino Ciccone and Mario Boccadoro and Anderson, {Kenneth Carl} and Barlogie, {Bart M} and Pieter Sonneveld and McCarthy, {Philip L}",
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Palumbo, A, Bringhen, S, Kumar, SK, Lupparelli, G, Usmani, SZ, Waage, A, Larocca, AT, Van Der Holt, BR, Musto, P, Offidani, M, Petrucci, MT, Evangelista, A, Zweegman, S, Nooka, AK, Spencer, A, Dimopoulos, MA, Hajek, R, Cavo, MM, Richardson, PG, Lonial, S, Ciccone, G, Boccadoro, M, Anderson, KC, Barlogie, BM, Sonneveld, P & McCarthy, PL 2014, 'Second primary malignancies with lenalidomide therapy for newly diagnosed myeloma: a meta-analysis of individual patient data' Lancet Oncology, vol. 15, no. 3, pp. 333 - 342. https://doi.org/10.1016/S1470-2045(13)70609-0

Second primary malignancies with lenalidomide therapy for newly diagnosed myeloma: a meta-analysis of individual patient data. / Palumbo, Antonio; Bringhen, Sara; Kumar, Shaji K; Lupparelli, Giulia; Usmani, Saad Zafar; Waage, Anders; Larocca, Alessandra T; Van Der Holt, Bronno R; Musto, Pellegrino; Offidani, Massimo; Petrucci, Maria Teresa; Evangelista, Andrea; Zweegman, Sonja; Nooka, Ajay K; Spencer, Andrew; Dimopoulos, Meletios Athanasios; Hajek, Roman; Cavo, Michele M; Richardson, Paul G; Lonial, Sagar; Ciccone, Giovannino; Boccadoro, Mario; Anderson, Kenneth Carl; Barlogie, Bart M; Sonneveld, Pieter; McCarthy, Philip L.

In: Lancet Oncology, Vol. 15, No. 3, 2014, p. 333 - 342.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Second primary malignancies with lenalidomide therapy for newly diagnosed myeloma: a meta-analysis of individual patient data

AU - Palumbo, Antonio

AU - Bringhen, Sara

AU - Kumar, Shaji K

AU - Lupparelli, Giulia

AU - Usmani, Saad Zafar

AU - Waage, Anders

AU - Larocca, Alessandra T

AU - Van Der Holt, Bronno R

AU - Musto, Pellegrino

AU - Offidani, Massimo

AU - Petrucci, Maria Teresa

AU - Evangelista, Andrea

AU - Zweegman, Sonja

AU - Nooka, Ajay K

AU - Spencer, Andrew

AU - Dimopoulos, Meletios Athanasios

AU - Hajek, Roman

AU - Cavo, Michele M

AU - Richardson, Paul G

AU - Lonial, Sagar

AU - Ciccone, Giovannino

AU - Boccadoro, Mario

AU - Anderson, Kenneth Carl

AU - Barlogie, Bart M

AU - Sonneveld, Pieter

AU - McCarthy, Philip L

PY - 2014

Y1 - 2014

N2 - Background: Lenalidomide has been linked to second primary malignancies in myeloma. We aimed to pool and analyse available data to compare the incidence of second primary malignancies in patients with and without lenalidomide exposure. Methods: We identified relevant studies through a search of PubMed and abstracts from the American Society of Clinical Oncology, American Society of Hematology, and the International Myeloma Workshop. Randomised, controlled, phase 3 trials that recruited patients with newly diagnosed multiple myeloma between Jan 1, 2000, and Dec 15, 2012, and in which at least one group received lenalidomide were eligible for inclusion. We obtained individual patient data (age, sex, date of diagnosis, allocated treatment and received treatment, duration of treatment and cause of discontinuation, maintenance treatment, date of first relapse, date of second primary malignancy diagnosis, type of second primary malignancy, date of death or last contact, and cause of death) by direct collaboration with the principal investigators of eligible trials. Primary outcomes of interest were cumulative incidence of all second primary malignancies, solid second primary malignancies, and haematological second primary malignancies, and were analysed by a one-step meta-analysis. Findings: We found nine eligible trials, of which seven had available data for 3254 patients. 3218 of these patients received treatment (2620 had received lenalidomide and 598 had not), and were included in our analyses. Cumulative incidences of all second primary malignancies at 5 years were 6?9 (95 CI 5?3-8?5) in patients who received lenalidomide and 4?8 (2?0-7?6) in those who did not (hazard ratio [HR] 1?55 [95 CI 1?03-2?34]; p=0?037). Cumulative 5-year incidences of solid second primary malignancies were 3?8 (95 CI 2?7-4?9) in patients who received lenalidomide and 3?4 (1?6-5?2) in those that did not (HR 1?1 [95 CI 0?62-2?00]; p=0?72), and of haematological second primary malignancies were 3?1 (95 CI 1?9-4?3) and 1?4 (0?0-3?6), respectively (HR 3?8 [95 CI 1?15-12?62]; p=0?029). Exposure to lenalidomide plus oral melphalan significantly increased haematological second primary malignancy risk versus melphalan alone (HR 4?86 [95 CI 2?79-8?46]; p

AB - Background: Lenalidomide has been linked to second primary malignancies in myeloma. We aimed to pool and analyse available data to compare the incidence of second primary malignancies in patients with and without lenalidomide exposure. Methods: We identified relevant studies through a search of PubMed and abstracts from the American Society of Clinical Oncology, American Society of Hematology, and the International Myeloma Workshop. Randomised, controlled, phase 3 trials that recruited patients with newly diagnosed multiple myeloma between Jan 1, 2000, and Dec 15, 2012, and in which at least one group received lenalidomide were eligible for inclusion. We obtained individual patient data (age, sex, date of diagnosis, allocated treatment and received treatment, duration of treatment and cause of discontinuation, maintenance treatment, date of first relapse, date of second primary malignancy diagnosis, type of second primary malignancy, date of death or last contact, and cause of death) by direct collaboration with the principal investigators of eligible trials. Primary outcomes of interest were cumulative incidence of all second primary malignancies, solid second primary malignancies, and haematological second primary malignancies, and were analysed by a one-step meta-analysis. Findings: We found nine eligible trials, of which seven had available data for 3254 patients. 3218 of these patients received treatment (2620 had received lenalidomide and 598 had not), and were included in our analyses. Cumulative incidences of all second primary malignancies at 5 years were 6?9 (95 CI 5?3-8?5) in patients who received lenalidomide and 4?8 (2?0-7?6) in those who did not (hazard ratio [HR] 1?55 [95 CI 1?03-2?34]; p=0?037). Cumulative 5-year incidences of solid second primary malignancies were 3?8 (95 CI 2?7-4?9) in patients who received lenalidomide and 3?4 (1?6-5?2) in those that did not (HR 1?1 [95 CI 0?62-2?00]; p=0?72), and of haematological second primary malignancies were 3?1 (95 CI 1?9-4?3) and 1?4 (0?0-3?6), respectively (HR 3?8 [95 CI 1?15-12?62]; p=0?029). Exposure to lenalidomide plus oral melphalan significantly increased haematological second primary malignancy risk versus melphalan alone (HR 4?86 [95 CI 2?79-8?46]; p

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JO - Lancet Oncology

JF - Lancet Oncology

SN - 1470-2045

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