Lenalidomide plus rituximab for the initial treatment of frail older patients with DLBCL: the FIL_ReRi phase 2 study

Author(s): Guido Gini1; Monica Tani2; Alessandra Tucci3; Luigi Marcheselli4; Marina Cesaretti4; Monica Bellei4; Anna Pascarella5; Filippo Ballerini6; Mauro Petrini1; Francesco Merli7; Attilio Olivieri1; Francesco Lanza2; Ombretta Annibali8; Vittorio Ruggero Zilioli9; Anna Marina Liberati10; Maria Chiara Tisi11; Annalisa Arcari12; Dario Marino13; Gerardo Musuraca14; Vincenzo Pavone15; Alberto Fabbri16; Samantha Pozzi17; Donato Mannina18; Caterina Plenteda19; Melania Celli20; Stefano Luminari7,21
Source: Blood (2023) 142 (17): 1438–1447
Maem Hussein MD

Dr. Maen Hussein's Thoughts

There are too many options for DLBCL now with monoclonal antibodies, bispecific and CAR-T therapy, but in frail patients, this might be an option. Tafatistamab with lenalidomide had higher ORR (55vs 50) and CR( 37 vs 27%) but this is comparing different trials, and this trial had mostly elderly pts, I do feel tafatistamab is fairly well tolerated though. But when in doubt this seems to be a fair option.


  • Rituximab and lenalidomide combination is feasible and has moderate activity in frontline therapy of frail older patients with DLBCL.
  • The FIL_ReRi trial represents a benchmark for future studies devised for frail patients with DLBCL.


Treatment of diffuse large B-cell lymphoma (DLBCL) in older patients is challenging, especially for those who are not eligible for anthracycline-containing regimens. Fondazione Italiana Linfomi (FIL) started the FIL_ReRi study, a 2-stage single-arm trial to investigate the activity and safety of the chemo-free combination of rituximab and lenalidomide (R2) in ≥70-year-old untreated frail patients with DLBCL. Frailty was prospectively defined using a simplified geriatric assessment tool. Patients were administered a maximum of 6 28-day cycles of 20 mg oral lenalidomide from days 2 to 22 and IV rituximab 375 mg/m2 on day 1, with response assessment after cycles 4 and 6. Patients with partial response or complete response (CR) at cycle 6 were administered lenalidomide 10 mg/d from days 1 to 21 for every 28 cycles for a total of 12 cycles or until progression or unacceptable toxicity. The primary end point was the overall response rate (ORR) after cycle 6; the coprimary end point was the rate of grade 3 or 4 extrahematological toxicity. The ORR was 50.8%, with 27.7% CR. After a median follow-up of 24 months, the median progression-free survival was 14 months, and the 2-year duration of response was 64%. Thirty-four patients experienced extrahematological toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events grade ≥3. The activity of the R2 combination was observed in a significant proportion of subjects, warranting further exploration of a chemo-free approach in frail older patients with DLBCL. This trial was registered at EudraCT as #2015-003371-29 and clinicaltrials.gov as #NCT02955823.

Author Affiliations

1Struttura Organizzativa Dipartimentale di Clinica Ematologica, Azienda Ospedaliero Universitaria delle Marche, Università Politecnica delle Marche, Ancona, Italy; 2Unità di Ematologia, Ospedale Santa Maria delle Croci, Ravenna, Italy; 3Unità di Ematologia, Azienda Socio Sanitaria Territoriale Spedali Civili di Brescia, Brescia, Italy; 4Uffici Studi Fondazione Italiana Linfomi, sede di Modena, Modena, Italy; 5Unità Operativa Complessa di Ematologia, Ospedale dell’Angelo, Venice-Mestre, Italy; 6Clinica Ematologica, IRCCS Ospedale Policlinico San Martino, Università di Genova, Genoa, Italy; 7Ematologia, Azienda Unità Sanitaria Locale – IRCCS, Reggio Emilia, Italy; 8Unità di Ematologia e Trapianto di Cellule Staminali, Università Campus Bio-Medico, Rome, Italy; 9Divisione di Ematologia, Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda, Milan, Italy; 10Struttura Complessa di Oncoematologia e Autotrapianto, Azienda Ospedaliera Santa Maria, Università degli Studi di Perugia, Terni, Italy; 11Ematologia, Ospedale San Bortolo, Azienda Unità Sanitaria Locale Socio Sanitaria 8 “Berica,” Vicenza, Italy; 12Unità di Ematologia, Ospedale Guglielmo da Saliceto, Piacenza, Italy; 13Oncologia 1, Istituto Oncologico Veneto IRCCS, Padua, Italy; 14Ematologia, IRCCS Istituto Romagnolo per lo Studio dei Tumori, Meldola, Italy; 15Unità Operativa Complessa di Ematologia e Trapianto, Ospedale Pia Fondazione Cardinale Panico, Tricase, Italy; 16Unità di Ematologia, Azienda Ospedaliero Universitaria Senese, Siena, Italy; 17Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell’Adulto, Università di Modena e Reggio Emilia, Centro Oncologico, Modena, Italy; 18Dipartimento di Oncoematologia, Ospedale Papardo, Messina, Italy; 19Unità Operativa di Ematologia e Centro Trapianti di Midollo Osseo, Azienda Ospedaliero Universitaria di Parma, Parma, Italy; 20Unità Operativa di Ematologia, Ospedale degli Infermi, Rimini, Italy; 21Dipartimento Chirurgico, Medico, Odontoiatrico e di Scienze Morfologiche con interesse Trapiantologico, Oncologico e di Medicina Rigenerativa, Università di Modena e Reggio Emilia, Reggio Emilia, Italy

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