Efficacy of bendamustine and rituximab as first salvage treatment in chronic lymphocytic leukemia and indirect comparison with ibrutinib: A GIMEMA, ERIC and UK CLL FORUM study

A Cuneo, G Follows, GM Rigolin, A Piciocchi, A Tedeschi, L Trentin, AM Perez, M Coscia, L Laurenti, G Musuraca, L Farina, AR Delgado, EM Orlandi, P Galieni, FR Mauro, C Visco, A Amendola, A Billio, R Marasca, A ChiarenzaV Meneghini, F Ilariucci, M Marchetti, S Molica, F Re, G Gaidano, M Gonzalez, F Forconi, S Ciolli, A Cortelezzi, M Montillo, L Smolej, A Schuh, TA Eyre, B Kennedy, KM Bowles, M Vignetti, J De La Serna, C Moreno, R Foà, P Ghia, European Research Initiative on CLL (ERIC) on behalf of the GIMEMA, UK CLL forum

Research output: Contribution to journalArticle

Abstract

We performed an observational study on the efficacy of bendamustine and rituximab (BR) as first salvage regimen in chronic lymphocytic leukemia (CLL). In an intention-to-treat analysis including 237 patients, the median progression-free survival (PFS) was 25 months. The presence of del (17p), unmutated IGHV and advanced stage were associated with a shorter PFS at multivariate analysis. The median time-to-next treatment was 31.3 months. Front-line treatment with a chemoimmunotherapy regimen was the only predictive factor for a shorter time to next treatment at multivariate analysis. The median overall survival (OS) was 74.5 months. Advanced disease stage (i.e. Rai stage III-IV or Binet stage C) and resistant disease were the only parameters significantly associated with a shorter OS. Grade 3-5 infections were recorded in 6.3% of patients. A matched-adjusted indirect comparison with ibrutinib given second-line within Named Patient Programs in the United Kingdom and in Italy was carried out with OS as objective end point. When restricting the analysis to patients with intact 17p who had received chemoimmunotherapy in first line, there was no difference in OS between patients treated with ibrutinib (63% alive at 36 months) and patients treated with BR (74.4% alive at 36 months). BR is an efficacious first salvage regimen in CLL in a real-life population, including the elderly and unfit patients. BR and ibrutinib may be equally effective in terms of OS when used as first salvage treatment in patients without 17p deletion. (Registered at clinicaltrials.gov identifier: 02491398). © 2018 Ferrata Storti Foundation.
Original languageEnglish
Pages (from-to)1209-1217
Number of pages9
JournalHaematologica
Volume103
Issue number7
DOIs
Publication statusPublished - 2018

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Salvage Therapy
B-Cell Chronic Lymphocytic Leukemia
Survival
Disease-Free Survival
Multivariate Analysis
Intention to Treat Analysis
PCI 32765
Rituximab
Bendamustine Hydrochloride
Italy
Observational Studies
Therapeutics
Infection

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Efficacy of bendamustine and rituximab as first salvage treatment in chronic lymphocytic leukemia and indirect comparison with ibrutinib: A GIMEMA, ERIC and UK CLL FORUM study. / Cuneo, A; Follows, G; Rigolin, GM; Piciocchi, A; Tedeschi, A; Trentin, L; Perez, AM; Coscia, M; Laurenti, L; Musuraca, G; Farina, L; Delgado, AR; Orlandi, EM; Galieni, P; Mauro, FR; Visco, C; Amendola, A; Billio, A; Marasca, R; Chiarenza, A; Meneghini, V; Ilariucci, F; Marchetti, M; Molica, S; Re, F; Gaidano, G; Gonzalez, M; Forconi, F; Ciolli, S; Cortelezzi, A; Montillo, M; Smolej, L; Schuh, A; Eyre, TA; Kennedy, B; Bowles, KM; Vignetti, M; De La Serna, J; Moreno, C; Foà, R; Ghia, P; on behalf of the GIMEMA, European Research Initiative on CLL (ERIC); forum, UK CLL.

In: Haematologica, Vol. 103, No. 7, 2018, p. 1209-1217.

Research output: Contribution to journalArticle

Cuneo, A, Follows, G, Rigolin, GM, Piciocchi, A, Tedeschi, A, Trentin, L, Perez, AM, Coscia, M, Laurenti, L, Musuraca, G, Farina, L, Delgado, AR, Orlandi, EM, Galieni, P, Mauro, FR, Visco, C, Amendola, A, Billio, A, Marasca, R, Chiarenza, A, Meneghini, V, Ilariucci, F, Marchetti, M, Molica, S, Re, F, Gaidano, G, Gonzalez, M, Forconi, F, Ciolli, S, Cortelezzi, A, Montillo, M, Smolej, L, Schuh, A, Eyre, TA, Kennedy, B, Bowles, KM, Vignetti, M, De La Serna, J, Moreno, C, Foà, R, Ghia, P, on behalf of the GIMEMA, ERIOCLLERIC & forum, UKCLL 2018, 'Efficacy of bendamustine and rituximab as first salvage treatment in chronic lymphocytic leukemia and indirect comparison with ibrutinib: A GIMEMA, ERIC and UK CLL FORUM study', Haematologica, vol. 103, no. 7, pp. 1209-1217. https://doi.org/10.3324/haematol.2018.189837
Cuneo, A ; Follows, G ; Rigolin, GM ; Piciocchi, A ; Tedeschi, A ; Trentin, L ; Perez, AM ; Coscia, M ; Laurenti, L ; Musuraca, G ; Farina, L ; Delgado, AR ; Orlandi, EM ; Galieni, P ; Mauro, FR ; Visco, C ; Amendola, A ; Billio, A ; Marasca, R ; Chiarenza, A ; Meneghini, V ; Ilariucci, F ; Marchetti, M ; Molica, S ; Re, F ; Gaidano, G ; Gonzalez, M ; Forconi, F ; Ciolli, S ; Cortelezzi, A ; Montillo, M ; Smolej, L ; Schuh, A ; Eyre, TA ; Kennedy, B ; Bowles, KM ; Vignetti, M ; De La Serna, J ; Moreno, C ; Foà, R ; Ghia, P ; on behalf of the GIMEMA, European Research Initiative on CLL (ERIC) ; forum, UK CLL. / Efficacy of bendamustine and rituximab as first salvage treatment in chronic lymphocytic leukemia and indirect comparison with ibrutinib: A GIMEMA, ERIC and UK CLL FORUM study. In: Haematologica. 2018 ; Vol. 103, No. 7. pp. 1209-1217.
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abstract = "We performed an observational study on the efficacy of bendamustine and rituximab (BR) as first salvage regimen in chronic lymphocytic leukemia (CLL). In an intention-to-treat analysis including 237 patients, the median progression-free survival (PFS) was 25 months. The presence of del (17p), unmutated IGHV and advanced stage were associated with a shorter PFS at multivariate analysis. The median time-to-next treatment was 31.3 months. Front-line treatment with a chemoimmunotherapy regimen was the only predictive factor for a shorter time to next treatment at multivariate analysis. The median overall survival (OS) was 74.5 months. Advanced disease stage (i.e. Rai stage III-IV or Binet stage C) and resistant disease were the only parameters significantly associated with a shorter OS. Grade 3-5 infections were recorded in 6.3{\%} of patients. A matched-adjusted indirect comparison with ibrutinib given second-line within Named Patient Programs in the United Kingdom and in Italy was carried out with OS as objective end point. When restricting the analysis to patients with intact 17p who had received chemoimmunotherapy in first line, there was no difference in OS between patients treated with ibrutinib (63{\%} alive at 36 months) and patients treated with BR (74.4{\%} alive at 36 months). BR is an efficacious first salvage regimen in CLL in a real-life population, including the elderly and unfit patients. BR and ibrutinib may be equally effective in terms of OS when used as first salvage treatment in patients without 17p deletion. (Registered at clinicaltrials.gov identifier: 02491398). {\circledC} 2018 Ferrata Storti Foundation.",
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T1 - Efficacy of bendamustine and rituximab as first salvage treatment in chronic lymphocytic leukemia and indirect comparison with ibrutinib: A GIMEMA, ERIC and UK CLL FORUM study

AU - Cuneo, A

AU - Follows, G

AU - Rigolin, GM

AU - Piciocchi, A

AU - Tedeschi, A

AU - Trentin, L

AU - Perez, AM

AU - Coscia, M

AU - Laurenti, L

AU - Musuraca, G

AU - Farina, L

AU - Delgado, AR

AU - Orlandi, EM

AU - Galieni, P

AU - Mauro, FR

AU - Visco, C

AU - Amendola, A

AU - Billio, A

AU - Marasca, R

AU - Chiarenza, A

AU - Meneghini, V

AU - Ilariucci, F

AU - Marchetti, M

AU - Molica, S

AU - Re, F

AU - Gaidano, G

AU - Gonzalez, M

AU - Forconi, F

AU - Ciolli, S

AU - Cortelezzi, A

AU - Montillo, M

AU - Smolej, L

AU - Schuh, A

AU - Eyre, TA

AU - Kennedy, B

AU - Bowles, KM

AU - Vignetti, M

AU - De La Serna, J

AU - Moreno, C

AU - Foà, R

AU - Ghia, P

AU - on behalf of the GIMEMA, European Research Initiative on CLL (ERIC)

AU - forum, UK CLL

PY - 2018

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N2 - We performed an observational study on the efficacy of bendamustine and rituximab (BR) as first salvage regimen in chronic lymphocytic leukemia (CLL). In an intention-to-treat analysis including 237 patients, the median progression-free survival (PFS) was 25 months. The presence of del (17p), unmutated IGHV and advanced stage were associated with a shorter PFS at multivariate analysis. The median time-to-next treatment was 31.3 months. Front-line treatment with a chemoimmunotherapy regimen was the only predictive factor for a shorter time to next treatment at multivariate analysis. The median overall survival (OS) was 74.5 months. Advanced disease stage (i.e. Rai stage III-IV or Binet stage C) and resistant disease were the only parameters significantly associated with a shorter OS. Grade 3-5 infections were recorded in 6.3% of patients. A matched-adjusted indirect comparison with ibrutinib given second-line within Named Patient Programs in the United Kingdom and in Italy was carried out with OS as objective end point. When restricting the analysis to patients with intact 17p who had received chemoimmunotherapy in first line, there was no difference in OS between patients treated with ibrutinib (63% alive at 36 months) and patients treated with BR (74.4% alive at 36 months). BR is an efficacious first salvage regimen in CLL in a real-life population, including the elderly and unfit patients. BR and ibrutinib may be equally effective in terms of OS when used as first salvage treatment in patients without 17p deletion. (Registered at clinicaltrials.gov identifier: 02491398). © 2018 Ferrata Storti Foundation.

AB - We performed an observational study on the efficacy of bendamustine and rituximab (BR) as first salvage regimen in chronic lymphocytic leukemia (CLL). In an intention-to-treat analysis including 237 patients, the median progression-free survival (PFS) was 25 months. The presence of del (17p), unmutated IGHV and advanced stage were associated with a shorter PFS at multivariate analysis. The median time-to-next treatment was 31.3 months. Front-line treatment with a chemoimmunotherapy regimen was the only predictive factor for a shorter time to next treatment at multivariate analysis. The median overall survival (OS) was 74.5 months. Advanced disease stage (i.e. Rai stage III-IV or Binet stage C) and resistant disease were the only parameters significantly associated with a shorter OS. Grade 3-5 infections were recorded in 6.3% of patients. A matched-adjusted indirect comparison with ibrutinib given second-line within Named Patient Programs in the United Kingdom and in Italy was carried out with OS as objective end point. When restricting the analysis to patients with intact 17p who had received chemoimmunotherapy in first line, there was no difference in OS between patients treated with ibrutinib (63% alive at 36 months) and patients treated with BR (74.4% alive at 36 months). BR is an efficacious first salvage regimen in CLL in a real-life population, including the elderly and unfit patients. BR and ibrutinib may be equally effective in terms of OS when used as first salvage treatment in patients without 17p deletion. (Registered at clinicaltrials.gov identifier: 02491398). © 2018 Ferrata Storti Foundation.

U2 - 10.3324/haematol.2018.189837

DO - 10.3324/haematol.2018.189837

M3 - Article

VL - 103

SP - 1209

EP - 1217

JO - Haematologica

JF - Haematologica

SN - 0390-6078

IS - 7

ER -