TKIs Do Not Add Protective Benefit Against Peripheral Neuropathy in Patients With ALL Receiving Vincristine

The addition of tyrosine kinase inhibitors (TKIs) to vincristine-based regimens did not result in significant differences in the occurrence of chemotherapy-induced peripheral neuropathy (CIPN) in patients with acute lymphoblastic leukemia (ALL), according to data presented at the 2022 ASH Annual Meeting.

Investigators presented findings in a poster, which showed that among patients who did and did not experienced chemotherapy-induced peripheral neuropathy, the only statistically significant variables were presence of baseline peripheral neuropathy and lower body mass index (P = .0092; P = .0359). Cumulative dosing, and total doses of vincristine were not found to be significant between these 2 groups (P = .2675; P = .0630).

Investigators reported trends toward lower rates of neuropathy in the TKI treatment arms vs the no TKI treatment arms, but this difference was not determined to be significant (P = .1027).

In addition, a sub-analysis of patients receiving hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone; n = 111) showed that 66% of patients in the TKI group developed neuropathy compared with 71.9% in the no TKI treatment group. This difference was also not found to be significant (P = .504).

In both the entire groups and in the hyper-CVAD subgroup, no significant differences were detected in maximum dose reductions, holds or cessations due to neuropathy, or worse grade seen between the groups.

In both analyses, the no TKI group also received higher cumulative doses and total doses of vincristine.

“Overall, we found no significant differences in the development of CIPN in patients with ALL treated with vincristine chemotherapy-based regimens with or without TKI, despite higher doses of vincristine chemotherapy based regimens utilized in patients treated without TKIs,” Michelle Fullmer, APRN-CNP, Division of Hematology, Department of Internal Medicine of The Ohio State University, and coinvestigators, wrote in the poster. “Future studies should focus on the impact of different TKIS for neuroprotection in the prevention of CIPN.”

ALL represents approximately 20% of acute leukemia diagnoses for adults, study authors noted in the poster. Vincristine-based regimens are considered the cornerstone of ALL treatments; however, these treatments are known to yield high rates of CIPN. TKIs have demonstrated a protective benefit against chemotherapy induced peripheral neuropathy and the study authors sought to evaluate whether these treatments would be effective in this setting.

Investigators retrospectively assessed the outcomes of adult patients with ALL patients who received vincristine-based chemotherapy regimens between January 1, 2011, and December 31, 2020, at the Ohio State University James Cancer Hospital. Investigators accounted age, gender, race, ethnicity, and relationship status, as well as clinical information, including drug and alcohol used, performance status, height and weight, ALL subtype, diagnosis date, chemotherapy regimen, comorbidities, falls, date of last follow-up, and information on CIPN.

The median patient age at diagnosis was 42 years (range, 17-80), the majority had B-cell ALL (75%), and the most common treatment regimen received was hyper CVAD (50.5%).

Patients were stratified by receipt of a tyrosine kinase inhibitor, and a sub-analysis was coincidence for patients who received hyper-CVAD based regimens.

Presence and severity of associated factors were assessed with the Wilxocin Rank-Sum test for numeric variables, and the chi-square test/Fishers exact test for categorical variables.

“Our retrospective study suggests a potential mechanistic difference of TKIs on the neuronal transport of vincristine, and this potential neuroprotective effect should be explored in future research,” co-investigator Gretchen A. McNally, PhD, ANP-BC, AOCNP, also of the Division of Hematology, Department of Internal Medicine of The Ohio State University, told Oncology Nursing News® in an interview. “This is exciting as VCR contributes to high rates of chemotherapy-induced peripheral neuropathy, negatively impacting quality of life.”

Reference

Sigmund AM, Fullmer M, Welkie RL, et al. Patterns of neuropathy in ALL patients treated with vincristine based regimens with and without tyrosine kinase inhibitors. Blood. 2022;140(suppl 1):5180-5182. doi:10.1182/blood-2022-166961