Lenalidomide consolidation benefits patients with CLL receiving chemoimmunotherapy: results for CALGB 10404 (Alliance)

John C. Byrd, Amy S. Ruppert, Nyla A. Heerema, Alese E. Halvorson, Eva Hoke, Mitchell R. Smith, John E. Godwin, Stephen Couban, Todd A. Fehniger, Michael J. Thirman, Martin S. Tallman, Frederick R. Appelbaum, Richard M. Stone, Sue Robinson, Julie E. Chang, Sumithra J Mandrekar, Richard A. Larson

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Abstract

Prior to novel targeted agents for chronic lymphocytic leukemia (CLL), the best chemoimmunotherapy regimen in patients with non-del(11q) disease was unclear. The role of lenalidomide was also not defined. This phase 2 study randomized 342 untreated patients with non-del(11q) CLL requiring therapy to fludarabine plus rituximab (FR; n = 123), FR plus lenalidomide consolidation (FR+L; n = 109), or FR plus cyclophosphamide (FCR; n = 110) and compared 2-year progression-free survival (PFS) rates of each to the historical control rate with FC (60%). Patients with del(11q) in at least 20% of pretreatment cells continued with FCR (n = 27) or were reassigned to FCR+L (n = 31) and excluded from the primary analysis. Among non-del(11q) patients, 2-year PFS rates were 64% (90% confidence interval [CI], 57-71; FR), 72% (90% CI, 65-79; FR+L), and 74% (90% CI, 66-80; FCR); FR+L and FCR had rates significantly greater than historical control. Median PFS was significantly shorter with FR compared with FR+L (P = .04) and FCR (P < .001): 43 (95% CI, 33-50), 61 (95% CI, 45-71), and 97 (95% CI, 61 to not reached) months, respectively. Median follow-up was 73 months and median overall survival (OS) was only reached with FCR (101 months; 95% CI, 96 to not reached). With FR+L, the risk of death decreased over time and was lower than with FR at later time points (P = .01), but not significantly different from FCR (P = .21). Future studies incorporating short courses of lenalidomide into other novel treatment regimens are justified.

Original languageEnglish (US)
Pages (from-to)1705-1718
Number of pages14
JournalBlood advances
Volume2
Issue number14
DOIs
StatePublished - Jul 24 2018

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B-Cell Chronic Lymphocytic Leukemia
Confidence Intervals
Disease-Free Survival
Survival Rate
lenalidomide
Cyclophosphamide
Survival
Therapeutics

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Byrd, J. C., Ruppert, A. S., Heerema, N. A., Halvorson, A. E., Hoke, E., Smith, M. R., ... Larson, R. A. (2018). Lenalidomide consolidation benefits patients with CLL receiving chemoimmunotherapy: results for CALGB 10404 (Alliance). Blood advances, 2(14), 1705-1718. https://doi.org/10.1182/bloodadvances.2017015396

Lenalidomide consolidation benefits patients with CLL receiving chemoimmunotherapy : results for CALGB 10404 (Alliance). / Byrd, John C.; Ruppert, Amy S.; Heerema, Nyla A.; Halvorson, Alese E.; Hoke, Eva; Smith, Mitchell R.; Godwin, John E.; Couban, Stephen; Fehniger, Todd A.; Thirman, Michael J.; Tallman, Martin S.; Appelbaum, Frederick R.; Stone, Richard M.; Robinson, Sue; Chang, Julie E.; Mandrekar, Sumithra J; Larson, Richard A.

In: Blood advances, Vol. 2, No. 14, 24.07.2018, p. 1705-1718.

Research output: Contribution to journalArticle

Byrd, JC, Ruppert, AS, Heerema, NA, Halvorson, AE, Hoke, E, Smith, MR, Godwin, JE, Couban, S, Fehniger, TA, Thirman, MJ, Tallman, MS, Appelbaum, FR, Stone, RM, Robinson, S, Chang, JE, Mandrekar, SJ & Larson, RA 2018, 'Lenalidomide consolidation benefits patients with CLL receiving chemoimmunotherapy: results for CALGB 10404 (Alliance)', Blood advances, vol. 2, no. 14, pp. 1705-1718. https://doi.org/10.1182/bloodadvances.2017015396
Byrd, John C. ; Ruppert, Amy S. ; Heerema, Nyla A. ; Halvorson, Alese E. ; Hoke, Eva ; Smith, Mitchell R. ; Godwin, John E. ; Couban, Stephen ; Fehniger, Todd A. ; Thirman, Michael J. ; Tallman, Martin S. ; Appelbaum, Frederick R. ; Stone, Richard M. ; Robinson, Sue ; Chang, Julie E. ; Mandrekar, Sumithra J ; Larson, Richard A. / Lenalidomide consolidation benefits patients with CLL receiving chemoimmunotherapy : results for CALGB 10404 (Alliance). In: Blood advances. 2018 ; Vol. 2, No. 14. pp. 1705-1718.
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abstract = "Prior to novel targeted agents for chronic lymphocytic leukemia (CLL), the best chemoimmunotherapy regimen in patients with non-del(11q) disease was unclear. The role of lenalidomide was also not defined. This phase 2 study randomized 342 untreated patients with non-del(11q) CLL requiring therapy to fludarabine plus rituximab (FR; n = 123), FR plus lenalidomide consolidation (FR+L; n = 109), or FR plus cyclophosphamide (FCR; n = 110) and compared 2-year progression-free survival (PFS) rates of each to the historical control rate with FC (60{\%}). Patients with del(11q) in at least 20{\%} of pretreatment cells continued with FCR (n = 27) or were reassigned to FCR+L (n = 31) and excluded from the primary analysis. Among non-del(11q) patients, 2-year PFS rates were 64{\%} (90{\%} confidence interval [CI], 57-71; FR), 72{\%} (90{\%} CI, 65-79; FR+L), and 74{\%} (90{\%} CI, 66-80; FCR); FR+L and FCR had rates significantly greater than historical control. Median PFS was significantly shorter with FR compared with FR+L (P = .04) and FCR (P < .001): 43 (95{\%} CI, 33-50), 61 (95{\%} CI, 45-71), and 97 (95{\%} CI, 61 to not reached) months, respectively. Median follow-up was 73 months and median overall survival (OS) was only reached with FCR (101 months; 95{\%} CI, 96 to not reached). With FR+L, the risk of death decreased over time and was lower than with FR at later time points (P = .01), but not significantly different from FCR (P = .21). Future studies incorporating short courses of lenalidomide into other novel treatment regimens are justified.",
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AU - Halvorson, Alese E.

AU - Hoke, Eva

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AU - Fehniger, Todd A.

AU - Thirman, Michael J.

AU - Tallman, Martin S.

AU - Appelbaum, Frederick R.

AU - Stone, Richard M.

AU - Robinson, Sue

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AU - Larson, Richard A.

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