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

Abstract

Background 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. Methods In 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. Results Five-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. Conclusion Replacement 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.

Vinorelbine causes a neuropathic pain-like state in mice via STING and MNK1 signaling associated with type I interferon induction

“…Among them vincristine causes the most severe neurotoxicity, 48 a deleterious effect also observed in preclinical studies on vincristine-induced peripheral neuropathy and mechanical allodynia, 49 but also in the clinical studies, resulting in peripheral neuropathy in 18%–70% of adult patients. 50 Compared to vincristine, vinorelbine is slightly less potent and less neurotoxic 48 and has a better therapeutic index than vincristine and vinblastine probably due to its higher affinity for mitotic microtubules. 51 Finally, vinorelbine treatment is associated with the worsening of peripheral neuropathy in patients with pre-existing diabetes or chemotherapy-induced peripheral neuropathy (CIPN).…”

Unusual Presentation of Acrodermatitis Chronica Atrophicans Resulting in Delay of Diagnosis and Inappropriate Treatment in Three Cases

“…Indeed, vincristine-induced peripheral neuropathy (VIPN), remains a major complication of lymphoma patients treated with CHOP. However, VIPN is commonly a sensorimotor neuropathy developing in almost all cases during treatment of lymphoma [21].…”

“…Other diagnostic tests include the lymphocyte transformation test and CD57+ natural killer cell determination. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Histopathologic findings may vary depending on where in the lesion the specimen is taken from, but they typically consist of superficial and deep perivascular and interstitial lymphocytic infiltrates with eosinophils centrally and with histiocytes and plasma cells at the periphery [23].…”

Cuproptosis-related lncRNA signature as a prognostic tool and therapeutic target in diffuse large B cell lymphoma

“…Vinorelbine induces cell cycle arrest in the G2-M phase, its inhibition leads to premature mitotic entry and cell death. Studies have shown that replacement of vincristine by vinorelbine due to neuropathy is effective and safe, which significantly improve neuropathy in patients compared to treatment with R-CHOP 56 . The regimen including rituximab, vinorelbine, ifosfamide, mitoxantrone and prednisone displays significant activity and acceptable toxicity in relapsed DLBCL 57 .…”