Skip to main content

L-PROBe: A Novel Non-anthracycline Combination Chemotherapy Regimen for Aggressive B Cell Non-Hodgkin Lymphoma in Elderly Patients


The management of aggressive B cell lymphomas in elderly patients is associated with poor tolerability of commonly used chemotherapeutic agents. The safety and tolerability of a novel combination chemotherapy regimen utilizing rituximab, lenalidomide, bendamustine, vincristine and prednisolone was assessed in a series of elderly patients with new onset or relapsed/refractory aggressive B cell lymphoma and inability to receive conventional chemotherapy due to poor performance status and/or significant comorbidities. Ten patients (7 male, 3 female) with a median age of 72 years (range 58–79 years) received therapy with lenalidomide (10 mg/day on days 1–14), rituximab (375 mg/m2 on day 1), bendamustine (90 mg/m2 on days 1 and 2), vincristine (1.4 mg/m2 on day 1) and prednisolone (60 mg/m2/day on days 1–5) with cycles repeated every 28 days. Grade 3/4 hematological toxicities included neutropenia (30 %), anemia (30 %) and thrombocytopenia (10 %). An overall response rate of 40 % was observed with a median survival of 120 days (range 14–286 days). Three of the patients who responded achieved complete remission at the end of six cycles of therapy. This combination chemotherapy appears to be well tolerated and effective in elderly patients with poor performance status. Larger controlled studies are indicated to clearly demonstrate applicability of this novel regimen.

This is a preview of subscription content, access via your institution.


  1. 1.

    Williams JN, Rai A, Lipscomb J, Koff JL, Nastoupil LJ, Flowers CR (2015) Disease characteristics, patterns of care, and survival in very elderly patients with diffuse large B-cell lymphoma. Cancer 121(11):1800–1808. doi:10.1002/cncr.29290

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Fischer K, Cramer P, Busch R, Stilgenbauer S, Bahlo J, Schweighofer CD et al (2011) Bendamustine combined with rituximab in patients with relapsed and/or refractory chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol Off J Am Soc Clin Oncol 29(26):3559–3566. doi:10.1200/JCO.2010.33.8061

    CAS  Article  Google Scholar 

  3. 3.

    Fowler N, Kahl BS, Lee P, Matous JV, Cashen AF, Jacobs SA et al (2011) Bortezomib, bendamustine, and rituximab in patients with relapsed or refractory follicular lymphoma: the phase II VERTICAL study. J Clin Oncol Off J Am Soc Clin Oncol 29(25):3389–3395. doi:10.1200/JCO.2010.32.1844

    CAS  Article  Google Scholar 

  4. 4.

    Ujjani C, Cheson B (2011) Efficacy of bendamustine in rituximab-refractory indolent B-cell non-Hodgkin lymphoma: review of a pivotal trial. Future Oncol 7(1):9–14. doi:10.2217/fon.10.169

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Cheson BD, Crawford J (2015) A phase I study of bendamustine, lenalidomide and rituximab in relapsed and refractory lymphomas. Br J Haematol 169(4):528–533. doi:10.1111/bjh.13321

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Wiernik PH, Lossos IS, Tuscano JM, Justice G, Vose JM, Cole CE et al (2008) Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin’s lymphoma. J Clin Oncol Off J Am Soc Clin Oncol 26(30):4952–4957. doi:10.1200/JCO.2007.15.3429

    Article  Google Scholar 

  7. 7.

    Nowakowski GS, LaPlant B, Habermann TM, Rivera CE, Macon WR, Inwards DJ et al (2011) Lenalidomide can be safely combined with R-CHOP (R2CHOP) in the initial chemotherapy for aggressive B-cell lymphomas: phase I study. Leukemia 25(12):1877–1881. doi:10.1038/leu.2011.165

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Zinzani PL, Pellegrini C, Derenzini E, Argnani L, Pileri S (2013) Long-term efficacy of the combination of lenalidomide and rituximab in elderly relapsed/refractory diffuse large B-cell lymphoma patients. Hematol Oncol 31(4):223–224. doi:10.1002/hon.2049

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Hitz F, Fischer N, Pabst T, Caspar C, Berthod G, Eckhardt K et al (2013) Rituximab, bendamustine, and lenalidomide in patients with aggressive B cell lymphoma not eligible for high-dose chemotherapy or anthracycline-based therapy: phase I results of the SAKK 38/08 trial. Ann Hematol 92(8):1033–1040. doi:10.1007/s00277-013-1751-z

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Vitolo U, Chiappella A, Franceschetti S, Carella AM, Baldi I, Inghirami G et al (2014) Lenalidomide plus R-CHOP21 in elderly patients with untreated diffuse large B-cell lymphoma: results of the REAL07 open-label, multicentre, phase 2 trial. Lancet Oncol 15(7):730–737. doi:10.1016/S1470-2045(14)70191-3

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Extermann M, Boler I, Reich RR, Lyman GH, Brown RH, DeFelice J et al (2012) Predicting the risk of chemotherapy toxicity in older patients: the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score. Cancer 118(13):3377–3386. doi:10.1002/cncr.26646

    Article  PubMed  Google Scholar 

  12. 12.

    Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grunhagen U, Losem C et al (2013) Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet 381(9873):1203–1210. doi:10.1016/S0140-6736(12)61763-2

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Chiappella A, Tucci A, Castellino A, Pavone V, Baldi I, Carella AM et al (2013) 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 98(11):1732–1738. doi:10.3324/haematol.2013.085134

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Harris AC, Jackson JM (1977) Lactulose in vincristine-induced constipation. Med J Aust 2(17):573–574

    CAS  PubMed  Google Scholar 

  15. 15.

    Witzig TE, Wiernik PH, Moore T, Reeder C, Cole C, Justice G et al (2009) Lenalidomide oral monotherapy produces durable responses in relapsed or refractory indolent non-Hodgkin’s Lymphoma. J Clin Oncol Off J Am Soc Clin Oncol 27(32):5404–5409. doi:10.1200/JCO.2008.21.1169

    CAS  Article  Google Scholar 

  16. 16.

    Wang M, Fowler N, Wagner-Bartak N, Feng L, Romaguera J, Neelapu SS et al (2013) Oral lenalidomide with rituximab in relapsed or refractory diffuse large cell, follicular and transformed lymphoma: a phase II clinical trial. Leukemia 27(9):1902–1909. doi:10.1038/leu.2013.95

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Davis CC, Cohen JB, Shah KS, Hutcherson DA, Surati MJ, Valla K et al (2015) Efficacy and tolerability of anthracycline-based therapy in elderly patients with diffuse large B-cell lymphoma. Clin Lymphoma Myeloma Leuk 15(5):270–277. doi:10.1016/j.clml.2014.12.011

    Article  PubMed  Google Scholar 

  18. 18.

    Witzig TE, Vose JM, Zinzani PL, Reeder CB, Buckstein R, Polikoff JA et al (2011) An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin’s lymphoma. Ann Oncol Off J Eur Soc Med Oncol ESMO 22(7):1622–1627. doi:10.1093/annonc/mdq626

    CAS  Article  Google Scholar 

  19. 19.

    Weidmann E, Neumann A, Fauth F, Atmaca A, Al-Batran SE, Pauligk C et al (2011) Phase II study of bendamustine in combination with rituximab as first-line treatment in patients 80 years or older with aggressive B-cell lymphomas. Ann Oncol Off J Eur Soc Med Oncol ESMO 22(8):1839–1844. doi:10.1093/annonc/mdq671

    CAS  Article  Google Scholar 

  20. 20.

    Rosenwald A, Wright G, Chan WC, Connors JM, Campo E, Fisher RI et al (2002) The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med 346(25):1937–1947. doi:10.1056/NEJMoa012914

    Article  PubMed  Google Scholar 

  21. 21.

    Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A et al (2000) Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403(6769):503–511. doi:10.1038/35000501

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Hernandez-Ilizaliturri FJ, Deeb G, Zinzani PL, Pileri SA, Malik F, Macon WR et al (2011) Higher response to lenalidomide in relapsed/refractory diffuse large B-cell lymphoma in nongerminal center B-cell-like than in germinal center B-cell-like phenotype. Cancer 117(22):5058–5066. doi:10.1002/cncr.26135

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Yang Y, Shaffer AL 3rd, Emre NC, Ceribelli M, Zhang M, Wright G et al (2012) Exploiting synthetic lethality for the therapy of ABC diffuse large B cell lymphoma. Cancer Cell 21(6):723–737. doi:10.1016/j.ccr.2012.05.024

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Nowakowski GS, LaPlant B, Macon WR, Reeder CB, Foran JM, Nelson GD et al (2015) 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. J Clin Oncol Off J Am Soc Clin Oncol 33(3):251–257. doi:10.1200/JCO.2014.55.5714

    CAS  Article  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Arjun Datt Law.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Law, A.D., Prakash, G., Khadwal, A. et al. L-PROBe: A Novel Non-anthracycline Combination Chemotherapy Regimen for Aggressive B Cell Non-Hodgkin Lymphoma in Elderly Patients. Indian J Hematol Blood Transfus 33, 61–68 (2017).

Download citation


  • Lymphoma
  • Lenalidomide
  • Bendamustine
  • Rituximab
  • Elderly