Hot Keywords
Tumor Microenvironment Exosomes and Extracellular Vesicles Breast Cancer Metastasis Bone Metastasis Metastatic Renal Cell Carcinoma Lymph node metastasis Mesothelioma Hematological Malignancies Thyroid Cancer Liquid Biopsies Early Diagnosis Lung Cancer Brain Tumors Lymphoma Oncolytic Virus Cervical Cancer Cancer Stem Cells

Top
J Cancer Metastasis Treat 2022;8:8. 10.20517/2394-4722.2021.153 © The Author(s) 2022.
Open Access Perspective

Moving towards the chemo-free treatment of lymphoma: hype or reality?

Scientific Advisor, Lymphoma Research Foundation, New York, NY 10005, USA.

Correspondence to: Prof. Bruce D. Cheson, Scientific Advisor, Lymphoma Research Foundation, New York, NY 10005, USA.E-mail: bdcheson@gmail.com

    Views:356 | Downloads:134 | Cited:0 | Comments:0 | :0
    Academic Editors: Lucio Miele, Rafat A. Siddiqui | Copy Editor: Xi-Jun Chen | Production Editor: Xi-Jun Chen

    © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

    Abstract

    A new generation of novel, effective targeted drugs and cellular therapies include monoclonal antibodies directed at the cell surface, such as the anti-CD-19 tafasitamab which, combined with lenalidomide, is the first therapy approved by the Food and Drug Administration for second-line treatment of diffuse large B-cell lymphoma. Other agents interfere with pro-survival intracellular signaling pathways including drugs that inhibit Bruton tyrosine kinase, phosphatidylinositol-3 kinase (PI3-kinase), and bcl-2. An increasing number of therapies impact the microenvironment, notably checkpoint inhibitors and bispecific antibodies. Chimeric antigen receptor-T cell therapy has improved the outcome of patients with a variety of histologies of lymphoma. Whereas in the past, such therapies would be used inrelapsed and refractory settings, they are now being evaluated as initial treatment in selected patients. With an improved ability to individualize treatment approaches, chemo-free will be a reality for lymphoma patients.

    BACKGROUND

    The beginnings of chemo-free approaches

    The possibility of treating diseases such as cancer with immunologic therapies dates back two centuries to the imagination of Pro. Paul Ehrlich, the father of modern immunology. Ehrlich[1] conceptualized the Magic Bullet, which bore a startling likeness to the structure of an antibody, that would attack the invaders while sparing normal cells. Nonetheless, it took more than a century for Kohler and Milstein[2] to develop the hybridoma technology that would enable the production of adequate quantities of monoclonal antibodies for clinical use and a few more years for Nadler et al.[3] to identify a suitable protein (B1, now known as CD20) on the malignant cell to target. After initial demonstrations of its activity in patients who had been previously treated[4,5], Ghielmini et al.[6] demonstrated impressive activity for the chimeric anti-CD20 monoclonal antibody rituximab in patients with and without prior therapy for their follicular lymphoma. Countless trials ensued, combining rituximab with various chemotherapy regimens as initial treatment of follicular and diffuse large B-cell lymphoma (DLBCL) and demonstrating a consistent survival advantage[7-10]. Meanwhile, in a parallel universe began the pursuit of a chemo-free approach. In 2003, investigators from what was then the Cancer and Leukemia Group B were the first to embark on a series of biological doublets, first with two monoclonal antibodies in previously untreated patients with follicular lymphoma: rituximab with the anti-CD80 galiximab[11] achieved an overall response rate (ORR) of 72%, with 48% complete remissions (CRs), with ORR and CR rates of 92% and 75%, 80% and 48%, and 55% and 27%, respectively, for low, intermediate, and high follicular lymphoma international prognostic index (FLIPI) scores. The progression-free survival for the low FLIPI patients was 75% at three years. Rituximab with the anti-CD22 epratuzumab[12] achieved an ORR of 87%, including 42% CRs. They next combined the anti-CD20 with the immunomodulatory agent lenalidomide, creating the regimen they called R2. Their first study in relapsed patients showed a significant benefit compared with lenalidomide alone[13]. When used as front-line therapy, each of these regimens was not only well-tolerated, but achieved response rates from 85%-95%[14], similar to what was achieved with chemoimmunotherapy regimens. Moreover, these responses were durable, many of which often lasting beyond a decade without recurrence. R2 was pursued by other investigators[15] and is now approved for relapsed and refractory follicular and other indolent non-Hodgkin lymphomas (NHL) based on data from the Augment trial[16]. In the front-line RELEVANCE trial, R2 showed similar efficacy with a more favorable toxicity profile compared with chemo-immunotherapy[17]. Unfortunately, the study did not meet its superiority endpoint.

    The next generation of chemo-free agents

    Over the last few years, a new wave of targeted agents has further enhanced interest in chemo-free approaches to lymphoid malignancies. A first-in-class oral inhibitor of activating mutation of Enhancer of zeste homolog 2, tazemetostat, offers a new option in patients with follicular lymphoma[18]. Impressive results with the covalent Bruton tyrosine kinase inhibitors such as ibrutinib, acalabrutinib, and zanubrutinib leukemia[19-24], and the non-covalent LOXO-305[25] have recreated the landscape for chronic lymphocytic leukemia (CLL) as well as other lymphoma histologies[26-30]. In addition, the bcl-2 inhibitor venetoclax has assumed a major role as a single agent, but more so in combinations[31,32]. Also active are the PI3k inhibitors idelalisib[33,34], copanlisib[35], duvelisib[36], and umbralisib[37]. As a result of these highly active, well-tolerated agents, CIT is now a blur in the rear view mirror for CLL and small lymphocytic lymphoma, patients with MYD88 mutated Waldenström macroglobulinemia, relapsed and refractory mantle cell lymphoma and marginal zone lymphomas. These therapies have rapidly moved to the front line in appropriate patients[31,32].

    Chemo-free agents for Hodgkin and aggressive lymphomas

    Now that we have taken care of the indolent diseases, at least for a while, what is the possibility of eschewing chemotherapy in the more aggressive histologies? For Hodgkin lymphoma, the universe shifted with the availability first of the antibody-drug conjugate brentuximab vedotin, and subsequently with the checkpoint inhibitors, nivolumab and pembrolizumab. After demonstrating single-agent activity in the relapsed refractory setting[33-40], these agents have been combined and sequenced with chemotherapy for relapsed/refractory patients as well as part of initial therapy[41,42]. Recently a trial of BV-Nivo in untreated HL patients who were older or considered unsuitable for chemotherapy, demonstrated a cure without chemotherapy[43].

    The last bastion appeared to be DLBCL. Aggressive diseases need aggressive treatment, right? Perhaps not! For patients who have already been failed by chemoimmunotherapy, repeating similar programs makes little sense. One of the newer regimens for relapsed or refractory DLBCL to even include a modest chemotherapy drug has been the combination of polatuzumab vedotin, the anti-CD79b antibody-drug conjugate, with bendamustine and rituximab, which has been approved in the United States as a third or subsequent line of therapy. Indeed, the new therapies have tended to rely more on targeted approaches. Indeed, the first regimen to be approved by the FDA for patients following a single prior line of therapy is L-MIND, the combination of the anti-CD19 monoclonal antibody tafasitamab with the immunomodulatory agent lenalidomide. This non-chemotherapeutic regimen achieves an overall response rate of 58% with 40% CRs, median duration of response of 34.6 months, with a median PFS of a year, at least as good as many multi-agent chemotherapy regimens in this setting[44]. More recently, loncastuximab tesirine, a CD-19 directed antibody-drug conjugate, was granted accelerated FDA approval for patients with relapsed and refractory DLBCL beyond the second line, based on the results of a multicentre phase II study LOTIS-2. The overall response rate was 48.3% with 24.1% CR rate and a median response duration of 10.3 months[45]. Selinexor, an oral inhibitor of nuclear transport protein exportin 1, induces responses in 28% of patients with 12% CR and a median duration of response of 9.3 months[46]. Based on these data from the SADAL trial, this drug was granted accelerated approval by the FDA for patients who have progressed following two or more lines of therapy. Although the single-agent results with this drug are modest, the drug has a promising future in combination with other drugs.

    The potential of new cellular and immunotherapies

    Presentations at the American Society of Hematology Annual Meeting in 2020 describing results with bispecific T-cell engagers and cellular therapies also strongly support a chemo-free future[47,48]. Not only does the CD3xCD20 bispecific mosunetuzumab exhibit activity in relapsed and refractory DLBCL and FL[49], but, in previously untreated, older, frail patients, it achieved responses in 57%-75% of patients, based on dose, including 37.5%-50% complete remissions, some of which were ongoing beyond a year[50]. Causing at least as much excitement were the results of ZUMA-12, a phase II study of the Chimeric antigen receptor-T (CAR-T) product axicaptagene ciloleucel as first-line therapy in patients with high-risk DLBCL characterized by being a high-grade B-cell NHL with MYC and BCL2 and/or Bcl-6 translocations, or an IPI score ≥ 3. The ORR was 85% with 74% CRs. 70% of responses were ongoing beyond the median follow-up of 9.3 months[51].

    Nonetheless, the road to a chemo-free world has not always been a smooth one[52]. In a number of instances, combining agents either with chemotherapy or even with others, each with a favorable safety profile led to life-threatening or even fatal toxicities. The experience with CAR-T has certainly been a steep learning curve. As more targeted drugs and cellular therapies become more readily available in general practice, the temptation to arbitrarily combine them in general practice will be powerful. However, multi-agent combinations must first be carefully monitored in clinical trials before subjecting patients to a risk of serious, unforeseen adverse effects.

    One chemo-free approach does not fit all

    Before we can totally banish chemoimmunotherapy from our armamentarium, a number of challenges must be overcome. First and foremost, biomarkers must be identified to help direct specific treatments to individual patients. Second, rather than what is usually empiric, targeted combinations should be based on sound scientific rationale for efficacy, with careful consideration for avoiding overlapping toxicities. Adaptive randomized trial design incorporating multiple arms and rapidly dropping those that fail to demonstrate sufficient efficacy or tolerability may help facilitate the completion of studies while preventing patients from receiving knowingly ineffective regimens.

    A number of assays are currently available to distinguish between patients with a high likelihood of responding to standard treatment versus those almost certainly to fail. Nonetheless, these patients are generally treated exactly the same. In the near future, patients will be assessed prior to therapy with respect to molecular signatures[53,54], circulating tumor DNA[55], total metabolic tumor volume[56], next-generation sequencing[57] and others to determine for whom conventional treatments are satisfactory, or, alternatively, which patients should be referred directly to investigational studies[58]. To be sure, the burgeoning number of increasingly effective drugs and cellular therapies should provide convincing evidence that patients with lymphoid malignancies can look forward to the reality of an improved outcome in a chemo-free world.

    DECLARATIONS

    Authors’ contributions

    The author contributed solely to the article.

    Availability of data and materials

    Not available.

    Financial support and sponsorship

    None.

    Conflicts of interest

    The author consults or participates in advisory boards with Abbvie, ADC Therapeutics, AstraZeneca, Beigene, Epizyme, Genmab, Incyte, Lilly, Morphosys, Karyopharm, Pharmacyclics, Kite, Merck, Symbio. He is on speakers bureaus for Beigene, Incyte, Morphosys.

    Ethical approval and consent to participate

    Not applicable.

    Consent for publication

    Not applicable.

    Copyright

    © The Author(s) 2022.

    References

    • 1. Ehrlich P. On immunity with special reference to the cell of life. Proc R Soc Lond (Biol) 1900;66:424-48.

      DOI
    • 2. Köhler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 1975;256:495-7.

      DOIPubMed
    • 3. Nadler LM, Ritz J, Hardy R, Pesando JM, Schlossman SF, Stashenko P. A unique cell surface antigen identifying lymphoid malignancies of B cell origin. J Clin Invest 1981;67:134-40.

      DOIPubMed PMC
    • 4. Maloney D, Liles T, Czerwinski D, et al. Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma. Blood 1994;84:2457-66.

      PubMed
    • 5. McLaughlin P, Grillo-López AJ, Link BK, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol 1998;16:2825-33.

      DOIPubMed
    • 6. Ghielmini M, Schmitz SF, Cogliatti SB, et al. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood 2004;103:4416-23.

      DOIPubMed
    • 7. Marcus R, Imrie K, Belch A, et al. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood 2005;105:1417-23.

      DOIPubMed
    • 8. Hiddemann W, Kneba M, Dreyling M, et al. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 2005;106:3725-32.

      DOIPubMed
    • 9. Herold M, Haas A, Srock S, et al. East German Study Group Hematology and Oncology Study. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol 2007;25:1986-92.

      DOIPubMed
    • 10. Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 2002;346:235-42.

      DOIPubMed
    • 11. Czuczman MS, Leonard JP, Johnson JL, et al. FLIPI score is applicable and predictive of response to upfront immunotherapy in CALGB 50402: phase II trial of extended induction galiximab ([G] anti-CD80 monoclonal antibody) plus rituximab [R]. Blood 2008;112:1003.

      DOI
    • 12. Grant BW, Jung SH, Johnson JL, et al. A phase 2 trial of extended induction epratuzumab and rituximab for previously untreated follicular lymphoma: CALGB 50701. Cancer 2013;119:3797-804.

      DOIPubMed PMC
    • 13. Leonard JP, Jung SH, Johnson J, et al. Randomized trial of lenalidomide alone versus lenalidomide plus rituximab in patients with recurrent follicular lymphoma: CALGB 50401 (Alliance). J Clin Oncol 2015;33:3635-40.

      DOIPubMed PMC
    • 14. Martin P, Jung SH, Pitcher B, et al. A phase II trial of lenalidomide plus rituximab in previously untreated follicular non-Hodgkin's lymphoma (NHL): CALGB 50803 (Alliance). Ann Oncol 2017;28:2806-12.

      DOIPubMed PMC
    • 15. Fowler NH, Davis RE, Rawal S, et al. Safety and activity of lenalidomide and rituximab in untreated indolent lymphoma: an open-label, phase 2 trial. Lancet Oncol 2014;15:1311-8.

      DOIPubMed PMC
    • 16. Leonard JP, Trneny M, Izutsu K, et al. AUGMENT Trial Investigators. AUGMENT: a Phase III Study of Lenalidomide plus Rituximab versus Placebo plus Rituximab in relapsed or refractory indolent lymphoma. J Clin Oncol 2019;37:1188-99.

      DOIPubMed PMC
    • 17. Morschhauser F, Fowler NH, Feugier P, et al. RELEVANCE Trial Investigators. Rituximab plus Lenalidomide in advanced untreated follicular lymphoma. N Engl J Med 2018;379:934-47.

      DOIPubMed
    • 18. Morschhauser F, Tilly H, Chaidos A, et al. Tazemetostat for patients with relapsed or refractory follicular lymphoma: an open-label, single-arm, multicentre, phase 2 trial. Lancet Oncol 2020;21:1433-42.

      DOIPubMed PMC
    • 19. Byrd JC, Furman RR, Coutre SE, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med 2013;369:32-42.

      DOIPubMed PMC
    • 20. O’brien S, Jones JA, Coutre SE, et al. Ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia with 17p deletion (RESONATE-17): a phase 2, open-label, multicentre study. Lancet Oncol 2016;17:1409-18.

      DOIPubMed
    • 21. Burger JA, Tedeschi A, Barr PM, et al. RESONATE-2 Investigators. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med 2015;373:2425-37.

      DOIPubMed PMC
    • 22. Byrd JC, Harrington B, O’Brien S, et al. Acalabrutinib (ACP-196) in relapsed chronic lymphocytic leukemia. N Engl J Med 2016;374:323-32.

      DOIPubMed PMC
    • 23. Sharman JP, Egyed M, Jurczak W, et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzumab for treatment-naive chronic lymphocytic leukaemia (ELEVATE-TN): a randomised, controlled, phase 3 trial. Lancet 2020;395:1278-91.

      DOI
    • 24. Hillmen P, Brown JR, Eichhorst BF, et al. ALPINE: zanubrutinib versus ibrutinib in relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma. Future Oncol 2020;16:517-23.

      DOIPubMed
    • 25. Mato AR, Shah NN, Jurczak W, et al. Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study. Lancet 2021;397:892-901.

      DOIPubMed
    • 26. Wang ML, Blum KA, Martin P, et al. Long-term follow-up of MCL patients treated with single-agent ibrutinib: updated safety and efficacy results. Blood 2015;126:739-45.

      DOIPubMed PMC
    • 27. Tam CS, Opat S, D’Sa S, et al. A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström macroglobulinemia: the ASPEN study. Blood 2020;136:2038-50.

      DOIPubMed PMC
    • 28. Wang M, Rule S, Zinzani PL, et al. Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. Lancet 2018;391:659-67.

      DOIPubMed PMC
    • 29. Owen RG, Mccarthy H, Rule S, et al. Acalabrutinib monotherapy in patients with Waldenström macroglobulinemia: a single-arm, multicentre, phase 2 study. Lancet Haematol 2020;7:e112-21.

      DOIPubMed
    • 30. Wang M, Shah NN, Alencar AJ, et al. LOXO-305, a next generation, highly selective, non-covalent BTK inhibitor in previously treated mantle cell lymphoma, Waldenström’s macroglobulinemia, and other non-Hodgkin lymphomas: results from the phase 1/2 BRUIN study. Blood 2020;136:8-10.

      DOI
    • 31. Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and Obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med 2019;380:2225-36.

      DOIPubMed
    • 32. Jain N, Keating M, Thompson P, et al. Ibrutinib and Venetoclax for first-line treatment of CLL. N Engl J Med 2019;380:2095-103.

      DOIPubMed
    • 33. Gopal AK, Kahl BS, de Vos S, et al. PI3Kδ inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med 2014;370:1008-18.

      DOIPubMed PMC
    • 34. Sharman JP, Coutre SE, Furman RR, et al. Final results of a randomized, phase III study of rituximab with or without idelalisib followed by open-label idelalisib in patients with relapsed chronic lymphocytic leukemia. J Clin Oncol 2019;37:1391-402.

      DOIPubMed
    • 35. Dreyling M, Santoro A, Mollica L, et al. Phosphatidylinositol 3-kinase inhibition by copanlisib in relapsed or refractory indolent lymphoma. J Clin Oncol 2017;35:3898-905.

      DOIPubMed
    • 36. Flinn IW, Miller CB, Ardeshna KM, et al. DYNAMO: a phase II study of duvelisib (IPI-145) in patients with refractory indolent non-Hodgkin lymphoma. J Clin Oncol 2019;37:912-22.

      DOIPubMed
    • 37. Lunning M, Vose J, Nastoupil L, et al. Ublituximab and umbralisib in relapsed/refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia. Blood 2019;134:1811-20.

      DOIPubMed PMC
    • 38. Younes A, Gopal AK, Smith SE, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol 2012;30:2183-9.

      DOIPubMed PMC
    • 39. Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med 2015;372:311-9.

      DOIPubMed PMC
    • 40. Armand P, Kuruvilla J, Michot JM, et al. KEYNOTE-013 4-year follow-up of pembrolizumab in classical Hodgkin lymphoma after brentuximab vedotin failure. Blood Adv 2020;4:2617-22.

      DOIPubMed PMC
    • 41. Allen PB, Savas H, Evens AM, et al. Pembrolizumab followed by AVD in untreated early unfavorable and advanced-stage classical Hodgkin lymphoma. Blood 2021;137:1318-26.

      DOIPubMed PMC
    • 42. Evens AM, Advani RH, Helenowski IB, et al. Multicenter phase II study of sequential Brentuximab Vedotin and Doxorubicin, Vinblastine, and Dacarbazine chemotherapy for older patients with untreated classical Hodgkin lymphoma. J Clin Oncol 2018;36:3015-22.

      DOIPubMed
    • 43. Cheson BD, Bartlett NL, Laplant B, et al. Brentuximab vedotin plus nivolumab as first-line therapy in older or chemotherapy-ineligible patients with Hodgkin lymphoma (ACCRU): a multicentre, single-arm, phase 2 trial. Lancet Haematol 2020;7:e808-15.

      DOIPubMed
    • 44. Salles G, Duell J, González Barca E, et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol 2020;21:978-88.

      DOIPubMed
    • 45. Caimi PF, Ai W, Alderuccio JP, et al. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol 2021;22:790-800.

      DOIPubMed
    • 46. Kalakonda N, Maerevoet M, Cavallo F, et al. Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): a single-arm, multinational, multicentre, open-label, phase 2 trial. Lancet Haematol 2020;7:e511-22.

      DOIPubMed
    • 47. Hutchings M, Mous R, Clausen MR, et al. Subcutaneous Epcoritamab induces complete responses with an encouraging safety profile across relapsed/refractory B-cell non-Hodgkin lymphoma subtypes, including patients with prior CAR-T therapy: updated dose escalation data. Blood 2020;136:45-6.

      DOI
    • 48. Hutchings M, Carlo-stella C, Bachy E, et al. Glofitamab step-up dosing induces high response rates in patients with hard-to-treat refractory or relapsed non-Hodgkin lymphoma. Blood 2020;136:46-8.

      DOI
    • 49. Assouline SE, Kim WS, Sehn LH, et al. Mosunetuzumab shows promising efficacy in patients with multiply relapsed follicular lymphoma: updated clinical experience from a phase I dose-escalation trial. Blood 2020;136:42-4.

      DOI
    • 50. Olszewski AJ, Avigdor A, Babu S, et al. Single-agent Mosunetuzumab is a promising safe and efficacious chemotherapy-free regimen for elderly/unfit patients with previously untreated diffuse large B-cell lymphoma. Blood 2020;136:43-5.

      DOI
    • 51. Neelapu SS, Dickinson M, Ulrickson ML, et al. Interim analysis of AZUMA-12: a phase 2 study of axicaptagene ciloleucel (Axi-Cel) as first-line therapy in patients (pts) with high-risk large B cell lymphoma (LBCL). Available from: https://ash.confex.com/ash/2020/webprogram/Paper134449.html [Last accessed on 3 Mar 2022].

    • 52. Cheson BD. Follicular lymphoma: is the road to cure paved with GALLIUM? Available from: https://ascopost.com/issues/december-10-2017/follicular-lymphoma-is-the-road-to-cure-paved-with-gallium/ [Last accessed on 3 Mar 2022].

    • 53. Chapuy B, Stewart C, Dunford AJ, et al. Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nat Med 2018;24:679-90.

      DOIPubMed PMC
    • 54. Schmitz R, Wright GW, Huang DW, et al. Genetics and pathogenesis of diffuse large B-cell lymphoma. N Engl J Med 2018;378:1396-407.

      DOIPubMed PMC
    • 55. Kurtz DM, Scherer F, Jin MC, et al. Circulating tumor DNA measurements as early outcome predictors in diffuse large B-cell lymphoma. J Clin Oncol 2018;36:2845-53.

      DOIPubMed PMC
    • 56. Meignan M, Cottereau AS, Versari A, et al. Baseline metabolic tumor volume predicts outcome in high-tumor-burden follicular lymphoma: a pooled analysis of three multicenter studies. J Clin Oncol 2016;34:3618-26.

      DOIPubMed
    • 57. Bolen CR, Klanova M, Trneny M, et al. Prognostic impact of somatic mutations in diffuse large B-cell lymphoma and relationship to cell-of-origin: data from the phase III GOYA study. Haematologica 2020;105:2298-307.

      DOIPubMed PMC
    • 58. Cheson BD. Predicting the future for DLBCL. Blood 2020;135:1308-9.

      DOIPubMed

    Cite This Article

    Cheson BD. Moving towards the chemo-free treatment of lymphoma: hype or reality?. J Cancer Metastasis Treat 2022;8:8. http://dx.doi.org/10.20517/2394-4722.2021.153

    Views
    356
    Downloads
    134
    Citations
     0
    Comments
    0

    0

    Comments

    Comments must be written in English. Spam, offensive content, impersonation, and private information will not be permitted. If any comment is reported and identified as inappropriate content by OAE staff, the comment will be removed without notice. If you have any queries or need any help, please contact us at support@oaepublish.com.

    © 2016-2022 OAE Publishing Inc., except certain content provided by third parties