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305 Lenalidomide and Rituximab (ReRi) As Front-Line Chemo-Free Therapy for Elderly Frail Patients with Diffuse Large B-Cell Lymphoma. a Phase II Study of the Fondazione Italiana Linfomi (FIL)Clinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 626. Aggressive Lymphomas Prospective Therapeutic Trials: Challenging Populations
Hematology Disease Topics & Pathways:
Clinical Trials, Biological, Lymphomas, Clinical Research, B Cell Lymphoma, Diseases, Aggressive Lymphoma, Therapies, Lymphoid Malignancies, Monoclonal Antibody Therapy
Saturday, December 11, 2021: 5:00 PM

Guido Gini1*, Monica Tani, MD2*, Renato Bassan, MD3*, Alessandra Tucci, MD4*, Filippo Ballerini5*, Michela Sampaolo6*, Francesco Merli, MD7*, Francesca Re8*, Attilio Olivieri, MD9, Mauro Petrini10*, Ombretta Annibali, MD, PhD11*, Anna Marina Liberati12*, Carlo Visco, MD13*, Annalisa Arcari14*, Sergio Storti, MD15, Alberto Fabbri, MD16*, Gerardo Musuraca17*, Vittorio Ruggero Zilioli, MD18*, M. Christina Cox, MD, PhD19 and Stefano Luminari20

1Hematology Clinic, AOU Ospedali Riuniti di Ancona, Ancona, Italy
2Hematology Unit, Ospedale Santa Maria delle Croci, Ravenna, Italy
3Ospedale dell'Angelo e SS. Giovanni e Paolo, Venezia Mestre, Italy
4Hematology, Department of Hematology, ASST Spedali Civili, Brescia, Italy
5IRCCS Ospedale Policlinico San Martino, Clinic of Hematology, Department of Internal Medicine (DiMI), Genova, Italy
6Hematology Clinic, A.O.U. Ospedali Riuniti, Ancona, Italy
7Hematology, AUSL-IRCCS, Reggio Emilia, Italy
8Division of Hematology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
9Ospedali Riuniti di Ancona, Clinic of Hematology, Ancona, Italy
10AOU Ospedali Riuniti di Ancona, Ancona, Italy
11Unit of Hematology, Stem Cell Transplantation, University Campus Bio Medico, Rome, Italy
12S.C. Oncoematologia, Università degli Studi di Perugia, A.O. Santa Maria, Terni, Italy
13Department of Medicine, Section of Hematology, University of Verona, Verona, Italy
1421Hematology Un it, Ospedale Guglielmo da Saliceto, Piacenza, Italy
15Oncoematologia, Fondazione di Ricerca e Cura Giovanni Paolo II, Campobasso, ITA
16Unit of Hematology, Azienda Ospedaliera Universitaria Senese, Siena, Italy
17Hematology Unit, IRCCS - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Meldola (FC), Italy
18Division of Hematology, ASST Grande Ospedale Metropolitano Niguarda, Milano, IT-MI, Italy
19Hematology, Sant'Andrea Hospital, Rome, Italy
20University of Modena and Reggio Emilia, Hematology, Arcispedale Santa Maria Nuova IRCCS, Reggio Emilia, Italy


Treatment of Diffuse Large B cell lymphoma (DLBCL) in the elderly population is challenging as many patients (pts) are not eligible to receive standard curative therapy, due to comorbid conditions and to a higher susceptibility to the side effects of standard anthracycline containing regimens.

Among currently available active drugs, Lenalidomide has been used in the setting of relapsed/refractory DLBCL both as monotherapy and in combination with rituximab, showing a good activity and an acceptable safety profile.

We started a prospective, multicenter, single arm, phase II trial to demonstrate activity and safety of a chemo-free combination of lenalidomide + rituximab in older (≥ 70 years) untreated pts with DLBCL who were prospectively defined as frail according to the simplified comprehensive geriatric assessment (sCGA) (Tucci A. et al., Leuk Lymphoma. 2015 Apr).


Pts were eligible if they were previously untreated DLBCL patients, older than 69 years and defined as frail according to sCGA.

The treatment consisted of a 28-day cycle (R2) combining oral Lenalidomide (20 mg on days 1 to 21) and i.v. Rituximab (375 mg/m2 on day 1); a maximum number of 6 cycles was planned; response assessment was performed after cycles 4 and 6. At the end of the 6th cycle, patients with partial or complete response continued treatment with Lenalidomide 10mg/d on days 1 to 21 every 28 days, until cycle 12 or unacceptable toxicity. Final response was evaluated within 28 days after the last study drug administration. Primary study endpoint was Overall Response Rate (ORR) after 6 R2 cycles, defined according to Lugano 2014 criteria; co-primary endpoint was the rate of extra-hematological toxicity with CTCAE grade >2 and of death for any cause during the treatment

The study was planned according to a two stage Simon design. A total of 68 pts had to be enrolled to complete the study. With 34 responses the study would be able to demonstrate the initial hypothesis of an improvement of response rate from 45% (p0) to 65% (P1)


From August 2018 to June 2021, 68 newly diagnosed frail DLBCL were enrolled in 18 Italian centers. Median age was 83 years (range 70-91) and 73% had stage III/IV; 57% had High risk IPI (i.e. 3-5 risk factors). 64 pts were confirmed eligible and started R2 treatment. The planned 6 courses of R2 were completed in 36 pts (56%). The median number of R2 cycles was 6 (1-6). Treatment was discontinued in 28 pts due to lymphoma progression (11 cases), extra-hematological toxicity (7), hematological toxicity (1), lost after 1 cycle and investigator choice after 5 cycles in CR in 1 case each, death in 7 cases (1 each for infection, pancytopenia, cachexia, ischemia and bowel infarction, and from unknown causes in 2 cases).

At the end of 6th R2 cycle 26 patients achieved a response (ORR 41%), 13 CR and 13 PR. After a median follow-up of 17 months, the overall survival, and progression free survival at 12 months were 69% (95CI 56-79%) and 55% (95%CI 42-66%), respectively. The duration of remission at 12 months was 72%.

Regarding safety 46 events were reported including 31 extra-hematological toxicities > CTCAE grade 2: 7 cardio-vascular (1 resulting in death), 4 nervous system disorders (1 resulting in death), 10 gastro-intestinal, 3 infections, 6 skin and subcutaneous tissue disorders, 5 respiratory events (all resolved). The rate of grade 3-4 adverse events was higher than the highest allowed limit of 28.


The Reri is the first study to evaluate activity and safety of a chemo-free therapy in patients with diffuse large B-Cell Lymphoma who are not eligible for conventional cytotoxic therapy. Even if this study was not able confirm the initial activity hypothesis, activity of the R2 combination was observed in a significant proportion of cases warranting further exploration of chemo-free approach of elderly frail patient with DLBCL.

Disclosures: Tucci: janssen: Membership on an entity's Board of Directors or advisory committees; Gentili: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Fabbri: Takeda: Honoraria; Servier/Pfizer: Honoraria; Takeda: Other: Travel, Accomodations, Expenses. Musuraca: janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Zilioli: Takeda: Other: travel expenses, accommodation; Gentili, Takeda, Gilead, Servier: Consultancy, Speakers Bureau; Roche, Italfarmaco: Consultancy, Honoraria; MSD, Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations. Luminari: Roche, Celgene, Teva Pharmaceuticals, Gilead Sciences, and Takeda Pharmaceuticals: Honoraria.

*signifies non-member of ASH