Frontline treatment with the combination obinutuzumab +/- chlorambucil for chronic lymphocytic leukemia outside clinical trials: Results of a multinational, multicenter study by ERIC and the Israeli CLL study group

HERISHANU, Y., A. SHAULOV, R. FINEMAN, S. BASIC-KINDA, A. AVIV, E. WASIK-SZCZEPANEK, O. JAKSIC, M. ZDRENGHEA, U. GREENBAUM, I. MANDAC, M. SIMKOVIC, M. MORAWSKA, O. BENJAMINI, M. SPACEK, A. NEMETS, O. BAIREY, L. TRENTIN, R. RUCHLEMER, L. LAURENTI, O. S. CIOCAN, Michael DOUBEK, L. SHVIDEL, N. DALI, F. MIRAS, A. DE METEUR, M. DIMOU, F. R. MAURO, M. COSCIA, H. BUMBEA, R. SZASZ, T. TADMOR, O. GUTWEIN, M. GENTILE, L. SCARF, A. TEDESCHI, P. SPORTOLETTI, E. GIMENO VAZQUEZ, J. MARQUET, S. ASSOULINE, M. PAPAIOANNOU, A. BRAESTER, L. LEVATO, M. GREGOR, G. M. RIGOLIN, J. LOSCERTALES, A. M. PEREZ, M. R. NIJZIEL, V. M. POPOV, R. COLLADO, I. SLAVUTSKY, G. ITCHAKI, S. RINGELSTEIN, N. GOLDSCHMIDT, C. PERRY, S. LEVI, A. POLLIACK a P. GHIA. Frontline treatment with the combination obinutuzumab +/- chlorambucil for chronic lymphocytic leukemia outside clinical trials: Results of a multinational, multicenter study by ERIC and the Israeli CLL study group. American Journal of Hematology. Hoboken: John Wiley & Sons, roč. 95, č. 6, s. 604-611. ISSN 0361-8609. doi:10.1002/ajh.25766. 2020.

Základní údaje

• Originální název: Frontline treatment with the combination obinutuzumab +/- chlorambucil for chronic lymphocytic leukemia outside clinical trials: Results of a multinational, multicenter study by ERIC and the Israeli CLL study group
• Autoři: HERISHANU, Y. (376 Izrael, garant), A. SHAULOV (376 Izrael), R. FINEMAN (376 Izrael), S. BASIC-KINDA (191 Chorvatsko), A. AVIV (376 Izrael), E. WASIK-SZCZEPANEK (376 Izrael), O. JAKSIC (191 Chorvatsko), M. ZDRENGHEA (642 Rumunsko), U. GREENBAUM (376 Izrael), I. MANDAC (191 Chorvatsko), M. SIMKOVIC (203 Česká republika), M. MORAWSKA (616 Polsko), O. BENJAMINI (376 Izrael), M. SPACEK (203 Česká republika), A. NEMETS (376 Izrael), O. BAIREY (376 Izrael), L. TRENTIN (380 Itálie), R. RUCHLEMER (376 Izrael), L. LAURENTI (380 Itálie), O. S. CIOCAN (642 Rumunsko), Michael DOUBEK (203 Česká republika, domácí), L. SHVIDEL (376 Izrael), N. DALI (376 Izrael), F. MIRAS (724 Španělsko), A. DE METEUR (56 Belgie), M. DIMOU (300 Řecko), F. R. MAURO (380 Itálie), M. COSCIA (380 Itálie), H. BUMBEA (642 Rumunsko), R. SZASZ (348 Maďarsko), T. TADMOR (376 Izrael), O. GUTWEIN (376 Izrael), M. GENTILE (380 Itálie), L. SCARF (380 Itálie), A. TEDESCHI (380 Itálie), P. SPORTOLETTI (380 Itálie), E. GIMENO VAZQUEZ (724 Španělsko), J. MARQUET (724 Španělsko), S. ASSOULINE (124 Kanada), M. PAPAIOANNOU (300 Řecko), A. BRAESTER (376 Izrael), L. LEVATO (380 Itálie), M. GREGOR (756 Švýcarsko), G. M. RIGOLIN (380 Itálie), J. LOSCERTALES (724 Španělsko), A. M. PEREZ (724 Španělsko), M. R. NIJZIEL (528 Nizozemské království), V. M. POPOV (642 Rumunsko), R. COLLADO (724 Španělsko), I. SLAVUTSKY (32 Argentina), G. ITCHAKI (376 Izrael), S. RINGELSTEIN (376 Izrael), N. GOLDSCHMIDT (376 Izrael), C. PERRY (376 Izrael), S. LEVI (376 Izrael), A. POLLIACK (376 Izrael) a P. GHIA (380 Itálie).
• Vydání: American Journal of Hematology, Hoboken, John Wiley & Sons, 2020, 0361-8609.

Další údaje

• Originální jazyk: angličtina
• Typ výsledku: Článek v odborném periodiku
• Obor: 30205 Hematology
• Stát vydavatele: Spojené státy
• Utajení: není předmětem státního či obchodního tajemství
• WWW: URL
• Impakt faktor: Impact factor: 10.047
• Kód RIV: RIV/00216224:14110/20:00116169
• Organizační jednotka: Lékařská fakulta
• Doi: http://dx.doi.org/10.1002/ajh.25766
• UT WoS: 000531328600013
• Klíčová slova anglicky: RITUXIMAB REGIMEN; THERAPY; CYCLOPHOSPHAMIDE; FLUDARABINE; IBRUTINIB
• Štítky: 14110212, rivok
• Příznaky: Mezinárodní význam, Recenzováno

Anotace

In recent years, considerable progress has been made in frontline therapy for elderly/physically unfit patients with CLL. The combination of obinutuzumab and chlorambucil (O-Clb) has been shown to prolong progression free survival (PFS, median PFS-31.5 months) and overall survival (OS) compared to chlorambucil alone. More recently, obinutuzumab given in combination with either ibrutinib or venetoclax improved PFS but not OS when compared to O-Clb. In this retrospective multinational, multicenter co-operative study, we evaluated the efficacy and safety of frontline treatment with O +/- Clb in unfit patients with CLL, in a "real-world" setting. Patients with documented del (17p13.1)/TP53 mutation were excluded. A total of 437 patients (median age, 75.9 years; median CIRS score, 8; median creatinine clearance, 61.1 mL/min) were included. The clinical overall response rate was 80.3% (clinical complete and partial responses in 38.7% and 41.6% of patients, respectively). Median observation time was 14.1 months and estimated median PFS was 27.6 months (95% CI, 24.2-31.0). In a multivariate analysis, high-risk disease [del (11q22.3) and/or IGHV-unmutated], lymph nodes of diameter > 5 cm, obinutuzumab monotherapy and reduced cumulative dose of obinutuzumab, were all independently associated with shorter PFS. The median OS has not yet been reached and estimated 2-year OS is 88%. In conclusion, in a "real-world" setting, frontline treatment with O-Clb achieves PFS comparable to that reported in clinical trials. Inferior outcomes were noted in patients with del (11q22.3) and/or unmutated IGHV and those treated with obinutuzumab-monotherapy. Thus, O-Clb can be still considered as legitimate frontline therapy for unfit CLL patients with low-risk disease.