Clinical features and management of GPRC5D-associated adverse events in novel GPRC5D × CD3 bispecific talquetamab-treated relapsed/refractory multiple myeloma patients: the MonumenTAL-1 China cohort experience.
An G, Jin J, et al. • Hematology (Amsterdam, Netherlands) • 2026
GPRC5D-associated on-target/off-tumor adverse events in Chinese RRMM patients treated with talquetamab were predominantly grade 1-2, well tolerated, and manageable with supportive therapies without need for dose modification in nearly all cases.
Key Findings
Methods
The MonumenTAL-1 China cohort included 41 adult Chinese patients with heavily pretreated relapsed/refractory multiple myeloma treated with subcutaneous talquetamab.
QW cohort: n=29 patients receiving 0.4 mg/kg once weekly
Median treatment duration was 7.7 months (QW cohort) and 7.1 months (Q2W cohort)
Median follow-up was 16.3 months (QW cohort) and 13.9 months (Q2W cohort)
Data cutoffs were 29 February 2024 (QW cohort) and 26 August 2024 (Q2W cohort)
Results
GPRC5D-associated on-target/off-tumor adverse events were predominantly grade 1-2 across both dosing cohorts.
Only one grade 3 adverse event was observed (non-rash skin toxicity in the QW cohort)
No grade 3 or higher GPRC5D-associated AEs were reported in the Q2W cohort
The severity profile was consistent with the known safety profile of talquetamab from the broader MonumenTAL-1 study
AEs were described as 'generally mild' and 'well tolerated'
Results
The most commonly observed GPRC5D-associated adverse events were oral AEs, skin AEs, and nail disorders.
Oral AEs included dysgeusia (taste disturbance) and dry mouth
Skin AEs included rash and non-rash skin toxicity
Nail disorders were also among the most common GPRC5D-associated AEs
These AE categories reflect off-tumor effects due to GPRC5D expression in normal tissues including skin, oral mucosa, and nails
Results
Between 50% and 100% of GPRC5D-associated adverse events had resolved by the respective data cutoffs.
Resolution rates ranged from 50% to 100% depending on the specific AE type
AEs were managed with supportive therapies
Talquetamab dose modification was needed in only one case (grade 2 weight decrease)
The high resolution rate supported the description of these AEs as manageable without treatment discontinuation in nearly all patients
Results
Talquetamab dose modification was required in only one patient out of 41, due to grade 2 weight decrease.
One patient in the combined cohorts required dose modification
The reason for dose modification was grade 2 weight decrease
No dose modifications were required for oral AEs, rash, or nail disorders despite their frequency
Supportive management without dose modification enabled prolonged treatment duration
Conclusions
Patient education prior to treatment initiation and timely management of GPRC5D-associated AEs were identified as important strategies to optimize talquetamab exposure and benefit.
The authors recommend educating patients with RRMM on potential GPRC5D-associated AEs before starting treatment
Timely management upon experiencing AEs was emphasized
Prolonged treatment was enabled by managing AEs with supportive therapies rather than dose modification
The safety profile in Chinese patients was consistent with the known global safety profile of talquetamab
What This Means
This research reports on the safety experience of 41 Chinese patients with relapsed or treatment-resistant multiple myeloma (a blood cancer) who were treated with talquetamab, a newer type of immunotherapy called a bispecific antibody. Talquetamab works by directing the immune system to attack cancer cells using a protein target called GPRC5D. Because this protein is also found in normal tissues like skin, mouth lining, and nails, the treatment can cause side effects in those areas. This study specifically examined those 'off-tumor' side effects in Chinese patients participating in a clinical trial called MonumenTAL-1.
This research suggests that the most common side effects were mild-to-moderate problems affecting the mouth (such as altered taste and dry mouth), skin (rashes and other skin changes), and nails. Importantly, only one patient experienced a severe (grade 3) side effect out of 41 patients, and only one patient needed a dose reduction — due to weight loss. Between half and all of the side effects resolved by the time the data were collected. Patients were treated for a median of about 7 months, and these side effects were managed with supportive care (such as moisturizers, mouth rinses, or other symptomatic treatments) rather than stopping or significantly reducing the cancer treatment.
This research suggests that although GPRC5D-targeted therapies like talquetamab do cause distinctive side effects related to their mechanism of action, these effects are generally manageable and do not usually require stopping treatment. The findings highlight the importance of telling patients what side effects to expect before they start therapy and addressing those side effects promptly when they occur. This approach may help patients stay on treatment longer and potentially get more benefit from it. The side effect profile seen in Chinese patients was similar to what has been observed in broader international trials, suggesting the findings are broadly applicable.
An G, Jin J, Cai Z, Jing H, Fu C, He P, et al.. (2026). Clinical features and management of GPRC5D-associated adverse events in novel GPRC5D × CD3 bispecific talquetamab-treated relapsed/refractory multiple myeloma patients: the MonumenTAL-1 China cohort experience.. Hematology (Amsterdam, Netherlands). https://doi.org/10.1080/16078454.2026.2702681