Vinorelbine as substitute for vincristine in patients with diffuse large B cell lymphoma and vincristine-induced neuropathy

Stefan Hatzl,Peter Neumeister,Maximilian Gornicec,Alexander Egle,Alexander Deutsch,Christine Beham-Schmid,Florian Posch,Werner Linkesch,Katharina T Prochazka,Theresa Magnes,Barbara Uhl,Thomas Melchardt,Arwin Rezai,Eduard Schulz,Richard Greil,Sandro Wangner,Hildegard Greinix

doi:10.1007/s00520-021-06059-2

Stefan Hatzl, Peter Neumeister + Show 15 more

Open Access

https://doi.org/10.1007/s00520-021-06059-2

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Abstract

BackgroundA combination of rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard first-line therapy for diffuse large B cell lymphoma (DLBCL), the most common aggressive lymphoma in adults. One of the major adverse effects of this regimen is vincristine-induced polyneuropathy which leads to discontinuation of vincristine in up to 30% of DLBCL-patients. Dose reduction of vincristine might worsen treatment outcomes of DLBCL but identification of treatment alternatives for patients exhibiting peripheral neuropathy during R-CHOP is an unmet need in hematology.MethodsIn this retrospective cohort study, comprising 987 patients with de novo DLBCL, we delineated the role of vinorelbine as a substitute for vincristine in R-CHOP by measuring improvements in neuropathy and outcome variables.ResultsFive-year overall survival (OS) and progression-free survival (PFS) were 72.6% and 63.1% in patients who received regular doses of vincristine, as compared to 60.6% and 51.7% in patients who received reduced doses of vincristine (p = 0.022 and p = 0.003, respectively). Of 199 patients who switched to vinorelbine, the majority experienced an improvement of neuropathy Furthermore, vinorelbine-switched patients showed favorable oncologic outcomes.ConclusionReplacement of vincristine by vinorelbine due to neuropathy is effective and safe, and results in a significant improvement in neuropathy as compared to treatment with R-CHOP.

Highlights

A combination of vincristine with cyclophosphamide, hydroxydaunorubicin, prednisone, and the monoclonal antibody rituximab (R-CHOP) administered in 21-day intervals is the standard of care and results in 5-year overall survival (OS) rates of up to 87% depending on risk factors [3, 4]
Evaluation of treatment outcomes after reduction of vincristine due to neuropathy First, we clarified whether the standard of care led to impaired outcomes
We analyzed 382 diffuse large B cell lymphoma (DLBCL) patients who were treated with RCHOP (“Salzburg cohort”)

Summary

Introduction

Diffuse large B cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma (NHL) in adults accounting for more than 30% of all NHL cases [1, 2]. Vincristine, a microtubule assembly inhibitor, has become an integral component of today’s treatment of DLBCL since its discovery as an active agent against lymphoma. Vincristine-induced peripheral neuropathy (VIPN), which is commonly a sensorimotor neuropathy, remains a major complication of lymphoma patients treated with R-CHOP. A combination of rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard first-line therapy for diffuse large B cell lymphoma (DLBCL), the most common aggressive lymphoma in adults. One of the major adverse effects of this regimen is vincristine-induced polyneuropathy which leads to discontinuation of vincristine in up to 30% of DLBCL-patients. Dose reduction of vincristine might worsen treatment outcomes of DLBCL but identification of treatment alternatives for patients exhibiting peripheral neuropathy during R-CHOP is an unmet need in hematology

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