Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma
Copyright © 2022 Massachusetts Medical Society..
BACKGROUND: G protein-coupled receptor, family C, group 5, member D (GPRC5D) is an orphan receptor expressed in malignant plasma cells. Talquetamab, a bispecific antibody against CD3 and GPRC5D, redirects T cells to mediate killing of GPRC5D-expressing myeloma cells.
METHODS: In a phase 1 study, we evaluated talquetamab administered intravenously weekly or every other week (in doses from 0.5 to 180 μg per kilogram of body weight) or subcutaneously weekly, every other week, or monthly (5 to 1600 μg per kilogram) in patients who had heavily pretreated relapsed or refractory multiple myeloma that had progressed with established therapies (a median of six previous lines of therapy) or who could not receive these therapies without unacceptable side effects. The primary end points - the frequency and type of dose-limiting toxic effects (study part 1 only), adverse events, and laboratory abnormalities - were assessed in order to select the recommended doses for a phase 2 study.
RESULTS: At the data-cutoff date, 232 patients had received talquetamab (102 intravenously and 130 subcutaneously). At the two subcutaneous doses recommended for a phase 2 study (405 μg per kilogram weekly [30 patients] and 800 μg per kilogram every other week [44 patients]), common adverse events were cytokine release syndrome (in 77% and 80% of the patients, respectively), skin-related events (in 67% and 70%), and dysgeusia (in 63% and 57%); all but one cytokine release syndrome event were of grade 1 or 2. One dose-limiting toxic effect of grade 3 rash was reported in a patient who had received talquetamab at the 800-μg dose level. At median follow-ups of 11.7 months (in patients who had received talquetamab at the 405-μg dose level) and 4.2 months (in those who had received it at the 800-μg dose level), the percentages of patients with a response were 70% (95% confidence interval [CI], 51 to 85) and 64% (95% CI, 48 to 78), respectively. The median duration of response was 10.2 months and 7.8 months, respectively.
CONCLUSIONS: Cytokine release syndrome, skin-related events, and dysgeusia were common with talquetamab treatment but were primarily low-grade. Talquetamab induced a substantial response among patients with heavily pretreated relapsed or refractory multiple myeloma. (Funded by Janssen Research and Development; MonumenTAL-1 ClinicalTrials.gov number, NCT03399799.).
Errataetall: |
CommentIn: N Engl J Med. 2022 Dec 15;387(24):2287-2290. - PMID 36507665 |
---|---|
Medienart: |
E-Artikel |
Erscheinungsjahr: |
2022 |
---|---|
Erschienen: |
2022 |
Enthalten in: |
Zur Gesamtaufnahme - volume:387 |
---|---|
Enthalten in: |
The New England journal of medicine - 387(2022), 24 vom: 15. Dez., Seite 2232-2244 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Chari, Ajai [VerfasserIn] |
---|
Links: |
---|
Themen: |
Antibodies, Bispecific |
---|
Anmerkungen: |
Date Completed 22.12.2022 Date Revised 27.12.2022 published: Print-Electronic ClinicalTrials.gov: NCT03399799 CommentIn: N Engl J Med. 2022 Dec 15;387(24):2287-2290. - PMID 36507665 Citation Status MEDLINE |
---|
doi: |
10.1056/NEJMoa2204591 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM350198691 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM350198691 | ||
003 | DE-627 | ||
005 | 20231226044442.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2022 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1056/NEJMoa2204591 |2 doi | |
028 | 5 | 2 | |a pubmed24n1167.xml |
035 | |a (DE-627)NLM350198691 | ||
035 | |a (NLM)36507686 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Chari, Ajai |e verfasserin |4 aut | |
245 | 1 | 0 | |a Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma |
264 | 1 | |c 2022 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 22.12.2022 | ||
500 | |a Date Revised 27.12.2022 | ||
500 | |a published: Print-Electronic | ||
500 | |a ClinicalTrials.gov: NCT03399799 | ||
500 | |a CommentIn: N Engl J Med. 2022 Dec 15;387(24):2287-2290. - PMID 36507665 | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2022 Massachusetts Medical Society. | ||
520 | |a BACKGROUND: G protein-coupled receptor, family C, group 5, member D (GPRC5D) is an orphan receptor expressed in malignant plasma cells. Talquetamab, a bispecific antibody against CD3 and GPRC5D, redirects T cells to mediate killing of GPRC5D-expressing myeloma cells | ||
520 | |a METHODS: In a phase 1 study, we evaluated talquetamab administered intravenously weekly or every other week (in doses from 0.5 to 180 μg per kilogram of body weight) or subcutaneously weekly, every other week, or monthly (5 to 1600 μg per kilogram) in patients who had heavily pretreated relapsed or refractory multiple myeloma that had progressed with established therapies (a median of six previous lines of therapy) or who could not receive these therapies without unacceptable side effects. The primary end points - the frequency and type of dose-limiting toxic effects (study part 1 only), adverse events, and laboratory abnormalities - were assessed in order to select the recommended doses for a phase 2 study | ||
520 | |a RESULTS: At the data-cutoff date, 232 patients had received talquetamab (102 intravenously and 130 subcutaneously). At the two subcutaneous doses recommended for a phase 2 study (405 μg per kilogram weekly [30 patients] and 800 μg per kilogram every other week [44 patients]), common adverse events were cytokine release syndrome (in 77% and 80% of the patients, respectively), skin-related events (in 67% and 70%), and dysgeusia (in 63% and 57%); all but one cytokine release syndrome event were of grade 1 or 2. One dose-limiting toxic effect of grade 3 rash was reported in a patient who had received talquetamab at the 800-μg dose level. At median follow-ups of 11.7 months (in patients who had received talquetamab at the 405-μg dose level) and 4.2 months (in those who had received it at the 800-μg dose level), the percentages of patients with a response were 70% (95% confidence interval [CI], 51 to 85) and 64% (95% CI, 48 to 78), respectively. The median duration of response was 10.2 months and 7.8 months, respectively | ||
520 | |a CONCLUSIONS: Cytokine release syndrome, skin-related events, and dysgeusia were common with talquetamab treatment but were primarily low-grade. Talquetamab induced a substantial response among patients with heavily pretreated relapsed or refractory multiple myeloma. (Funded by Janssen Research and Development; MonumenTAL-1 ClinicalTrials.gov number, NCT03399799.) | ||
650 | 4 | |a Clinical Trial, Phase I | |
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 7 | |a Antibodies, Bispecific |2 NLM | |
650 | 7 | |a GPRC5D protein, human |2 NLM | |
650 | 7 | |a Receptors, G-Protein-Coupled |2 NLM | |
650 | 7 | |a CD3 Complex |2 NLM | |
700 | 1 | |a Minnema, Monique C |e verfasserin |4 aut | |
700 | 1 | |a Berdeja, Jesus G |e verfasserin |4 aut | |
700 | 1 | |a Oriol, Albert |e verfasserin |4 aut | |
700 | 1 | |a van de Donk, Niels W C J |e verfasserin |4 aut | |
700 | 1 | |a Rodríguez-Otero, Paula |e verfasserin |4 aut | |
700 | 1 | |a Askari, Elham |e verfasserin |4 aut | |
700 | 1 | |a Mateos, María-Victoria |e verfasserin |4 aut | |
700 | 1 | |a Costa, Luciano J |e verfasserin |4 aut | |
700 | 1 | |a Caers, Jo |e verfasserin |4 aut | |
700 | 1 | |a Verona, Raluca |e verfasserin |4 aut | |
700 | 1 | |a Girgis, Suzette |e verfasserin |4 aut | |
700 | 1 | |a Yang, Shiyi |e verfasserin |4 aut | |
700 | 1 | |a Goldsmith, Rachel B |e verfasserin |4 aut | |
700 | 1 | |a Yao, Xiang |e verfasserin |4 aut | |
700 | 1 | |a Pillarisetti, Kodandaram |e verfasserin |4 aut | |
700 | 1 | |a Hilder, Brandi W |e verfasserin |4 aut | |
700 | 1 | |a Russell, Jeffery |e verfasserin |4 aut | |
700 | 1 | |a Goldberg, Jenna D |e verfasserin |4 aut | |
700 | 1 | |a Krishnan, Amrita |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t The New England journal of medicine |d 1945 |g 387(2022), 24 vom: 15. Dez., Seite 2232-2244 |w (DE-627)NLM000008184 |x 1533-4406 |7 nnns |
773 | 1 | 8 | |g volume:387 |g year:2022 |g number:24 |g day:15 |g month:12 |g pages:2232-2244 |
856 | 4 | 0 | |u http://dx.doi.org/10.1056/NEJMoa2204591 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 387 |j 2022 |e 24 |b 15 |c 12 |h 2232-2244 |