Efficacy and Safety Profile of Lenalidomide vs Lenalidomide + R-CHOP in patients with Diffuse Large B Cell Lymphoma: A Systematic Review

Lenalidomide vs Lenalidomide + R-CHOP


  • Muhammad Sajjad Ali Ayub Medical College, Abbottabad, Pakistan
  • Shahzaib Maqbool Rawalpindi Medical University, Rawalpindi, Pakistan
  • Azeen Razzaq Rawalpindi Medical University, Rawalpindi, Pakistan
  • Abdur Rehman Rawalpindi Medical University, Rawalpindi, Pakistan
  • Salman Yousaf Services Institute of Medical Sciences, Lahore, Pakistan
  • Muhammad Farhan Rawalpindi Medical University, Rawalpindi, Pakistan
  • Maryam Farhan Baloch Allama Iqbal Medical College, Lahore, Pakistan
  • Muhammad Abdul Khaliq Khan Baqai Medical university, Karachi, Pakistan




DLBCL, Lenalidomide, Lenalidomide R-CHOP


The most frequent cause of non-Hodgkin lymphoma, which accounts for around one-third of cases, is diffuse large B cell lymphoma (DLBCL). Immune chemotherapy combined with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard therapy for DLBCL. Objective: To analysing the utilization of Lenalidomide versus Lenalidomide R-CHOP regimen in treatment of DLBCL in terms of treatment efficacy and safety. Methods: PRISMA guidelines were followed for conducting this study. A thorough literature search was done from November 15 to November 25, 2022. A variety of databases, including PubMed, Google Scholar, and other, were used to conduct the literature search. Finally, for this systematic review, 10 studies were chosen. Results: In our study the monotherapy with Lenalidomide was found less significant in terms of improvement in Overall response rate, complete response among patients with DLBCL. However; Lenalidomide + R-CHOP was more effective in improving overall response rate (ORR) with ORR of 92.89% vs 30.58% and complete response rate (CRR) of 80.20% vs 12.53%. The partial response rate (PR) was comparable between two therapies.  similarly, the Progression free survival was also better in combination therapy. Haematological and Non-Hematological adverse effects of grade >3 were found higher among patients with combination therapy and Neutropenia was commonly observed adverse effect. Conclusions: Combination therapy was associated with significant improvement in disease outcome, however; the adverse effects were reported high in combination therapy vs monotherapy.



Cabanillas F and Shah B. Advances in diagnosis and management of diffuse large B-cell lymphoma. Clinical Lymphoma Myeloma and Leukemia. 2017 Dec; 17(12): 783-96. doi: 10.1016/j.clml.2017.10.007. DOI: https://doi.org/10.1016/j.clml.2017.10.007

Castellino A, Chiappella A, LaPlant BR, Pederson LD, Gaidano G, Macon WR, et al. Lenalidomide plus R-CHOP21 in newly diagnosed diffuse large B-cell lymphoma (DLBCL): long-term follow-up results from a combined analysis from two phase 2 trials. Blood Cancer Journal. 2018 Nov; 8(11): 108. doi: 10.1038/s41408-018-0145-9. DOI: https://doi.org/10.1038/s41408-018-0145-9

Gandhi AK, Kang J, Naziruddin S, Parton A, Schafer PH, Stirling DI. Lenalidomide inhibits proliferation of Namalwa CSN. 70 cells and interferes with Gab1 phosphorylation and adaptor protein complex assembly. Leukemia Research. 2006 Jul; 30(7): 849-58. doi: 10.1016/j.leukres.2006.01.010. DOI: https://doi.org/10.1016/j.leukres.2006.01.010

Garciaz S, Coso D, Schiano de Colella JM, Bouabdallah R. Lenalidomide for the treatment of B-cell lymphoma. Expert Opinion on Investigational Drugs. 2016 Sep; 25(9): 1103-16. doi: 10.1080/13543784.2016.1208170. DOI: https://doi.org/10.1080/13543784.2016.1208170

Grygorowicz MA, Borycka IS, Nowak E, Paszkiewicz-Kozik E, Rymkiewicz G, Błachnio K, et al. Lenalidomide potentiates CD4+ CD25+ Treg-related suppression of lymphoma B-cell proliferation. Clinical and Experimental Medicine. 2017 May; 17: 193-207. doi: 10.1007/s10238-016-0411-8. DOI: https://doi.org/10.1007/s10238-016-0411-8

Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004 Jan; 103(1):275-82. doi: 10.1182/blood-2003-05-1545. DOI: https://doi.org/10.1182/blood-2003-05-1545

Li S, Young KH, Medeiros LJ. Diffuse large B-cell lymphoma. Pathology. 2018 Jan; 50(1): 74-87. doi: 10.1016/j.pathol.2017.09.006. DOI: https://doi.org/10.1016/j.pathol.2017.09.006

Schoenbeck KL and Wildes TM. Updated perspectives on the management of multiple myeloma in older patients: focus on lenalidomide. Clinical Interventions in Aging. 2020 May: 619-33. doi: 10.2147/CIA.S196087. DOI: https://doi.org/10.2147/CIA.S196087

Vose JM, Habermann TM, Czuczman MS, Zinzani PL, Reeder CB, Tuscano JM, et al. Single‐agent lenalidomide is active in patients with relapsed or refractory aggressive non‐Hodgkin lymphoma who received prior stem cell transplantation. British Journal of Haematology. 2013 Sep; 162(5): 639-47. doi: 10.1111/bjh.12449. DOI: https://doi.org/10.1111/bjh.12449

Wu L, Adams M, Carter T, Chen R, Muller G, Stirling D, et al. Lenalidomide enhances natural killer cell and monocyte-mediated antibody-dependent cellular cytotoxicity of rituximab-treated CD20+ tumor cells. Clinical Cancer Research. 2008 Jul; 14(14): 4650-7. doi: 10.1158/1078-0432.CCR-07-4405. DOI: https://doi.org/10.1158/1078-0432.CCR-07-4405

Oremus M, Oremus C, Hall GB, McKinnon MC, ECT & Cognition Systematic Review Team. Inter-rater and test-retest reliability of quality assessments by novice student raters using the Jadad and Newcastle-Ottawa Scales. BMJ Open. 2012 Jul; 2(4): e001368. doi: 10.1136/bmjopen-2012-001368. DOI: https://doi.org/10.1136/bmjopen-2012-001368

Mondello P, Steiner N, Willenbacher W, Ferrero S, Ghione P, Marabese A, et al. Lenalidomide in relapsed or refractory diffuse large B-cell lymphoma: is it a valid treatment option? The Oncologist. 2016 Sep; 21(9): 1107-12. doi:10.1634/theoncologist.2016-0103. DOI: https://doi.org/10.1634/theoncologist.2016-0103

Witzig TE, Vose JM, Zinzani PL, Reeder CB, Buckstein R, Polikoff JA, et al. An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin’s lymphoma. Annals of Oncology. 2011 Jul; 22(7): 1622-7. doi:10.1093/annonc/mdq626. DOI: https://doi.org/10.1093/annonc/mdq626

Wiernik PH, Lossos IS, Tuscano JM, Justice G, Vose JM, Cole CE, et al. Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin's lymphoma. Journal of Clinical Oncology. 2008 Oct; 26(30): 4952-7. doi:10.1200/JCO.2007.15.3429. DOI: https://doi.org/10.1200/JCO.2007.15.3429

Czuczman MS, Trněný M, Davies A, Rule S, Linton KM, Wagner-Johnston N, et al. A phase 2/3 multicenter, randomized, open-label study to compare the efficacy and safety of lenalidomide versus investigator's choice in patients with relapsed or refractory diffuse large B-cell lymphoma. Clinical Cancer Research. 2017 Aug; 23(15): 4127-37. doi: 10.1158/1078-0432.CCR-16-2818. DOI: https://doi.org/10.1158/1078-0432.CCR-16-2818

Beylot-Barry M, Mermin D, Maillard A, Bouabdallah R, Bonnet N, Duval-Modeste AB, et al. A single-arm phase II trial of lenalidomide in relapsing or refractory primary cutaneous large B-cell lymphoma, leg type. Journal of Investigative Dermatology. 2018 Sep; 138(9): 1982-9. doi: 10.1016/j.jid.2018.03.1516. DOI: https://doi.org/10.1016/j.jid.2018.03.1516

Desai SH, LaPlant B, Macon WR, King RL, Wang Y, Inwards DJ, et al. Lenalidomide in combination with R-CHOP produces high response rates and progression-free survival in new, untreated diffuse large B-cell lymphoma transformed from follicular lymphoma: results from the Phase 2 MC078E study. Blood Cancer Journal. 2021 Sep; 11(9): 160. doi: 10.1038/s41408-021-00542-z. DOI: https://doi.org/10.1038/s41408-021-00542-z

Nowakowski GS, LaPlant B, Macon WR, Reeder CB, Foran JM, Nelson GD, et al. Lenalidomide combined with R-CHOP overcomes negative prognostic impact of non-germinal center B-cell phenotype in newly diagnosed diffuse large B-Cell lymphoma: a phase II study. Journal of Clinical Oncology. 2015 Jan; 33(3): 251-7. doi: 10.1200/JCO.2014.55.5714. DOI: https://doi.org/10.1200/JCO.2014.55.5714

Nowakowski GS, LaPlant B, Habermann TM, Rivera CE, Macon WR, Inwards DJ, et al. Lenalidomide can be safely combined with R-CHOP (R2CHOP) in the initial chemotherapy for aggressive B-cell lymphomas: phase I study. Leukemia. 2011 Dec; 25(12): 1877-81. doi: 10.1038/leu.2011.165. DOI: https://doi.org/10.1038/leu.2011.165

Vitolo U, Chiappella A, Franceschetti S, Carella AM, Baldi I, Inghirami G, et al. Lenalidomide plus R-CHOP21 in elderly patients with untreated diffuse large B-cell lymphoma: results of the REAL07 open-label, multicentre, phase 2 trial. The Lancet Oncology. 2014 Jun; 15(7): 730-7. doi: 10.1016/S1470-2045(14)70191-3. DOI: https://doi.org/10.1016/S1470-2045(14)70191-3

Chiappella A, Tucci A, Castellino A, Pavone V, Baldi I, Carella AM, et al. Lenalidomide plus cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab is safe and effective in untreated, elderly patients with diffuse large B-cell lymphoma: a phase I study by the Fondazione Italiana Linfomi. haematologica. 2013 Nov; 98(11): 1732. doi: 10.3324/haematol.2013.085134. DOI: https://doi.org/10.3324/haematol.2013.085134

Teras LR, DeSantis CE, Cerhan JR, Morton LM, Jemal A, Flowers CR. 2016 US lymphoid malignancy statistics by World Health Organization subtypes. CA: a cancer journal for clinicians. 2016 Nov; 66(6): 443-59. doi: 10.3322/caac.21357. DOI: https://doi.org/10.3322/caac.21357

Friedberg JW. Relapsed/refractory diffuse large B-cell lymphoma. Hematology 2010, the American Society of Hematology Education Program Book. 2011 Dec; 2011(1): 498-505. doi: 10.1182/asheducation-2011.1.498. DOI: https://doi.org/10.1182/asheducation-2011.1.498

Wang M, Fowler N, Wagner-Bartak N, Feng L, Romaguera J, Neelapu SS, et al. Oral lenalidomide with rituximab in relapsed or refractory diffuse large cell, follicular and transformed lymphoma: a phase II clinical trial. Leukemia. 2013 Sep; 27(9): 1902-9. doi: 10.1038/leu.2013.95. DOI: https://doi.org/10.1038/leu.2013.95

Goy A, Sinha R, Williams ME, Besisik SK, Drach J, Ramchandren R, et al. Single-agent lenalidomide in patients with mantle-cell lymphoma who relapsed or progressed after or were refractory to bortezomib: phase II MCL-001 (EMERGE) study. Journal of Clinical Oncology. 2013 Oct; 31(29): 3688. doi: 10.1200/JCO.2013.49.2835. DOI: https://doi.org/10.1200/JCO.2013.49.2835

Thieblemont C, Tilly H, Gomes da Silva M, Casasnovas RO, Fruchart C, Morschhauser F, et al. Lenalidomide maintenance compared with placebo in responding elderly patients with diffuse large B-cell lymphoma treated with first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. Journal of Clinical Oncology. 2017 Aug; 35(22): 2473-81. doi: 10.1200/JCO.2017.72.6984. DOI: https://doi.org/10.1200/JCO.2017.72.6984

Nowakowski GS, Chiappella A, Gascoyne RD, Scott DW, Zhang Q, Jurczak W, et al. ROBUST: a phase III study of lenalidomide plus R-CHOP versus placebo plus R-CHOP in previously untreated patients with ABC-type diffuse large B-cell lymphoma. Journal of Clinical Oncology. 2021 Apr; 39(12): 1317. doi: 10.1200/JCO.20.01366. DOI: https://doi.org/10.1200/JCO.20.01366



DOI: 10.54393/pjhs.v4i08.947
Published: 2023-08-31

How to Cite

Ali, M. S., Maqbool, S. ., Razzaq, A., Rehman, A. ., Yousaf, S. ., Farhan, M. ., Farhan Baloch, M. ., & Khaliq Khan, M. A. . (2023). Efficacy and Safety Profile of Lenalidomide vs Lenalidomide + R-CHOP in patients with Diffuse Large B Cell Lymphoma: A Systematic Review: Lenalidomide vs Lenalidomide + R-CHOP. Pakistan Journal of Health Sciences, 4(08), 71–77. https://doi.org/10.54393/pjhs.v4i08.947



Systematic Review


Most read articles by the same author(s)