Weight loss and dysgeusia in relapsed/refractory multiple myeloma patients treated with talquetamab

Abstract Talquetamab is an approved therapy for relapsed multiple myeloma. This study examined dysgeusia and weight loss occurrences, alongside investigating symptom reversibility post‐treatment cessation. Dysgeusia was prevalent, persisting in 15% of patients. On average, patients lost 6% of their weight during treatment, with weight loss persisting in about half of the patients post‐discontinuation. Weight loss and dysgeusia are important adverse events to consider while on talquetamab treatment. Extending dose intervals can potentially prevent such adverse events and should be studied in future prospective clinical trials.

Extending dose intervals can potentially prevent such adverse events and should be studied in future prospective clinical trials.

K E Y W O R D S
dysgeusia, multiple myeloma, talquetamab, weight loss Talquetamab, an approved bispecific monoclonal antibody, binds to both the G-protein coupled receptor family C group 5 member D (GPRC5D) receptor on myeloma cells and the CD3 receptor on T cells, offering a targeted therapy option for patients with relapsed refractory multiple myeloma (RRMM).It has demonstrated high response rates in heavily pretreated RRMM patients [1][2][3].The expression of GPRC5D extends to both malignant and non-malignant plasma cells, as well as healthy tissues like the epithelial cells of the tongue [2,4].Patients undergoing treatment with talquetamab commonly experience skin and nail complications, along with taste disturbances, possibly linked to the expression of GPRC5D in hard keratin-producing cells.This localized expression likely explains the potential mechanism behind dysgeusia observed with talquetamab administration.Limited information exists regarding the extent of weight loss and alterations in taste associated with the administration of talquetamab.In the MonumentaL-1 study, 30% of patients have decreased weight and 63% of patients have dysgeusia with subcutaneous talquetamab and all of the events were of low grade [4].In addition, it is not well under- stood whether these side effects are reversible upon discontinuation of treatment.The objective of this study was to assess the occurrence of dysgeusia and weight loss in patients undergoing treatment with talquetamab, as well as to investigate the reversibility of these symptoms after treatment cessation.
The study involved patients diagnosed with RRMM who received at least one dose of talquetamab at the University of Arkansas for Medical Sciences until December 2022.Data collected retrospectively included patient demographics, baseline disease characteristics, prior therapies, number of talquetamab doses administered, and adverse events (AEs) such as weight loss, dysgeusia, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and other side effects.AEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE), with dysgeusia categorized into grades 1 and 2. Additionally, a Body Mass Index-Adjusted Weight Loss Grading System (BMI-WLGS) was employed to monitor weight loss trends during treatment [5].Percentage weight loss (%WL) was calculated using the formula [ and one patient had grade IV weight loss per the BMI-WLGS grading system.Weight loss was calculated using data from all patients, including those who did not lose weight.Fourteen patients (82%) reported dysgeusia during talquetamab treatment (Table 2).Eight of these patients had grade I dysgeusia, and six patients had grade II dysgeusia.Two patients had persistent dysgeusia for more than 4 months even after discontinuation of talquetamab treatment at the time of the last follow-up.Eight patients had weight gain after talquetamab discontinuation (n = 8/14, 57%), with five returning to their baseline weight or higher.Six of these patients had dysgeusia during talquetamab, and all six had resolution of dysgeusia after talquetamab discontinuation.We found no correlation between longer time of therapy and severity of weight loss.The median follow up time while on talquetamab was 6.73 months, ranging from 2.07 to 17.71, IQR 9.82.Median progression-free survival (PFS) was 6.74 months from initiation of talquetamab.No difference in PFS was found between patients who developed dysgeusia and patients who did not develop dysgeusia.
This study demonstrates the prevalence of weight loss and dysgeusia caused by talquetamab use.In prior studies, the most common treatment-emergent AEs with talquetamab were CRS, cytopenia, and dermatologic toxicities and the majority of them were of low grade [4].It is important to note that the dysgeusia grading system only has grades I and II.
Our study results showed that more than two-thirds of patients treated with talquetamab developed BMI-adjusted WLGS grade ≥II and dysgeusia (Figures S1 and S2).Patients, on average, lost 6% of their initial weight during talquetamab treatment.Weight loss persisted in approximately half of the patients after discontinuation of talquetamab.A recent study assessed the safety and efficacy of reduced-intensity dosing with talquetamab in patients with RRMM.
Patients were enrolled in the MonumenTAL-1 trial, and those who switched to less frequent or reduced dosing with talquetamab were evaluated.Results showed that most patients who switched to reduced dosing maintained or deepened their responses to talquetamab, and AEs generally improved over time, however, weight loss didn't improve despite less frequent or reduced dosing.These findings suggest that reduced or less frequent dosing of talquetamab may help mitigate AE while sustaining treatment response, warranting further investigation into its clinical implications [6].
Another study aimed to investigate the impact of talquetamab therapy on taste perception, salivary flow, dry mouth sensation, and quality of life in patients with RRMM.Using pre-and post-treatment assessments, eight RRMM patients were evaluated for changes in taste perception, salivary flow rates, dry mouth sensation, and overall quality of life following initiation of talquetamab therapy.The results revealed a rapid and significant decrease in taste perception scores and exacerbated dry mouth sensation in all patients, despite no observed change in salivary flow rates.These oral toxicities were found to significantly impair patients' overall quality of life, highlighting the importance of proactive management strategies to address these adverse effects and optimize treatment outcomes [7].
Our findings underscore the importance of discussing and monitoring weight loss while undergoing talquetamab treatment This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
© 2024 The Author(s).eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.
Patient baseline characteristics at the initiation of talquetamab.
Dysgeusia and body mass index (BMI)-adjusted weight loss grading system.Samer Al Hadidi conceived the research idea.Syed Naqvi and Asis Shrestha worked on data collection.Samer Al Hadidi and Syed Naqvi wrote the initial draft.All authors critically reviewed and approved the final submission of the manuscript.
. Such treatment-emergent AEs need to be discussed with patients and monitored during treatment.Identifying and addressing weight loss and dysgeusia early while on talquetamab treatment with extended dose intervals can potentially prevent additional complications (including oropharyngeal infections and nutritional deficiencies) and discomfort.Future trials may investigate the role of various supportive measures, TA B L E 2