Daratumumab plus lenalidomide and dexamethasone for untreated Myeloma

MAIA Trial Investigators

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

BACKGROUND: Lenalidomide plus dexamethasone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation. We sought to determine whether the addition of daratumumab would significantly reduce the risk of disease progression or death in this population.

METHODS: We randomly assigned 737 patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation to receive daratumumab plus lenalidomide and dexamethasone (daratumumab group) or lenalidomide and dexamethasone alone (control group). Treatment was to continue until the occurrence of disease progression or unacceptable side effects. The primary end point was progression-free survival.

RESULTS: At a median follow-up of 28.0 months, disease progression or death had occurred in 240 patients (97 of 368 patients [26.4%] in the daratumumab group and 143 of 369 patients [38.8%] in the control group). The estimated percentage of patients who were alive without disease progression at 30 months was 70.6% (95% confidence interval [CI], 65.0 to 75.4) in the daratumumab group and 55.6% (95% CI, 49.5 to 61.3) in the control group (hazard ratio for disease progression or death, 0.56; 95% CI, 0.43 to 0.73; P<0.001). The percentage of patients with a complete response or better was 47.6% in the daratumumab group and 24.9% in the control group (P<0.001). A total of 24.2% of the patients in the daratumumab group, as compared with 7.3% of the patients in the control group, had results below the threshold for minimal residual disease (1 tumor cell per 10 5 white cells) (P<0.001). The most common adverse events of grade 3 or 4 were neutropenia (50.0% in the daratumumab group vs. 35.3% in the control group), anemia (11.8% vs. 19.7%), lymphopenia (15.1% vs. 10.7%), and pneumonia (13.7% vs. 7.9%).

CONCLUSIONS: Among patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation, the risk of disease progression or death was significantly lower among those who received daratumumab plus lenalidomide and dexamethasone than among those who received lenalidomide and dexamethasone alone. A higher incidence of neutropenia and pneumonia was observed in the daratumumab group. (Funded by Janssen Research and Development; MAIA ClinicalTrials.gov number, NCT02252172.).

OriginalsprogEngelsk
TidsskriftNew England Journal of Medicine
Vol/bind380
Udgave nummer22
Sider (fra-til)2104-2115
ISSN0028-4793
DOI
StatusUdgivet - 30. maj 2019

Fingeraftryk

Control Groups
Confidence Intervals
Neutropenia
daratumumab
Lymphopenia
Residual Neoplasm
Disease-Free Survival
Incidence
Research
Population
Neoplasms

Citer dette

MAIA Trial Investigators. / Daratumumab plus lenalidomide and dexamethasone for untreated Myeloma. I: New England Journal of Medicine. 2019 ; Bind 380, Nr. 22. s. 2104-2115.
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title = "Daratumumab plus lenalidomide and dexamethasone for untreated Myeloma",
abstract = "BACKGROUND: Lenalidomide plus dexamethasone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation. We sought to determine whether the addition of daratumumab would significantly reduce the risk of disease progression or death in this population.METHODS: We randomly assigned 737 patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation to receive daratumumab plus lenalidomide and dexamethasone (daratumumab group) or lenalidomide and dexamethasone alone (control group). Treatment was to continue until the occurrence of disease progression or unacceptable side effects. The primary end point was progression-free survival.RESULTS: At a median follow-up of 28.0 months, disease progression or death had occurred in 240 patients (97 of 368 patients [26.4{\%}] in the daratumumab group and 143 of 369 patients [38.8{\%}] in the control group). The estimated percentage of patients who were alive without disease progression at 30 months was 70.6{\%} (95{\%} confidence interval [CI], 65.0 to 75.4) in the daratumumab group and 55.6{\%} (95{\%} CI, 49.5 to 61.3) in the control group (hazard ratio for disease progression or death, 0.56; 95{\%} CI, 0.43 to 0.73; P<0.001). The percentage of patients with a complete response or better was 47.6{\%} in the daratumumab group and 24.9{\%} in the control group (P<0.001). A total of 24.2{\%} of the patients in the daratumumab group, as compared with 7.3{\%} of the patients in the control group, had results below the threshold for minimal residual disease (1 tumor cell per 10 5 white cells) (P<0.001). The most common adverse events of grade 3 or 4 were neutropenia (50.0{\%} in the daratumumab group vs. 35.3{\%} in the control group), anemia (11.8{\%} vs. 19.7{\%}), lymphopenia (15.1{\%} vs. 10.7{\%}), and pneumonia (13.7{\%} vs. 7.9{\%}). CONCLUSIONS: Among patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation, the risk of disease progression or death was significantly lower among those who received daratumumab plus lenalidomide and dexamethasone than among those who received lenalidomide and dexamethasone alone. A higher incidence of neutropenia and pneumonia was observed in the daratumumab group. (Funded by Janssen Research and Development; MAIA ClinicalTrials.gov number, NCT02252172.).",
keywords = "Aged, Aged, 80 and over, Antibodies, Monoclonal/administration & dosage, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Dexamethasone/administration & dosage, Female, Humans, Lenalidomide/administration & dosage, Male, Middle Aged, Multiple Myeloma/drug therapy, Neutropenia/chemically induced, Progression-Free Survival",
author = "T. Facon and Shaji Kumar and T. Plesner and Orlowski, {R. Z.} and P. Moreau and N. Bahlis and S. Basu and H. Nahi and C. Hulin and H. Quach and H. Goldschmidt and M. O’Dwyer and A. Perrot and Venner, {C. P.} and K. Weisel and Mace, {J. R.} and N. Raje and M. Attal and M. Tiab and M. Macro and L. Frenzel and X. Leleu and T. Ahmadi and C. Chiu and J. Wang and Rampelbergh, {R. Van} and Uhlar, {C. M.} and R. Kobos and M. Qi and Usmani, {S. Z.} and {MAIA Trial Investigators}",
year = "2019",
month = "5",
day = "30",
doi = "10.1056/NEJMoa1817249",
language = "English",
volume = "380",
pages = "2104--2115",
journal = "The New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachusetts Medical Society",
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}

Daratumumab plus lenalidomide and dexamethasone for untreated Myeloma. / MAIA Trial Investigators.

I: New England Journal of Medicine, Bind 380, Nr. 22, 30.05.2019, s. 2104-2115.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Daratumumab plus lenalidomide and dexamethasone for untreated Myeloma

AU - Facon, T.

AU - Kumar, Shaji

AU - Plesner, T.

AU - Orlowski, R. Z.

AU - Moreau, P.

AU - Bahlis, N.

AU - Basu, S.

AU - Nahi, H.

AU - Hulin, C.

AU - Quach, H.

AU - Goldschmidt, H.

AU - O’Dwyer, M.

AU - Perrot, A.

AU - Venner, C. P.

AU - Weisel, K.

AU - Mace, J. R.

AU - Raje, N.

AU - Attal, M.

AU - Tiab, M.

AU - Macro, M.

AU - Frenzel, L.

AU - Leleu, X.

AU - Ahmadi, T.

AU - Chiu, C.

AU - Wang, J.

AU - Rampelbergh, R. Van

AU - Uhlar, C. M.

AU - Kobos, R.

AU - Qi, M.

AU - Usmani, S. Z.

AU - MAIA Trial Investigators

PY - 2019/5/30

Y1 - 2019/5/30

N2 - BACKGROUND: Lenalidomide plus dexamethasone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation. We sought to determine whether the addition of daratumumab would significantly reduce the risk of disease progression or death in this population.METHODS: We randomly assigned 737 patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation to receive daratumumab plus lenalidomide and dexamethasone (daratumumab group) or lenalidomide and dexamethasone alone (control group). Treatment was to continue until the occurrence of disease progression or unacceptable side effects. The primary end point was progression-free survival.RESULTS: At a median follow-up of 28.0 months, disease progression or death had occurred in 240 patients (97 of 368 patients [26.4%] in the daratumumab group and 143 of 369 patients [38.8%] in the control group). The estimated percentage of patients who were alive without disease progression at 30 months was 70.6% (95% confidence interval [CI], 65.0 to 75.4) in the daratumumab group and 55.6% (95% CI, 49.5 to 61.3) in the control group (hazard ratio for disease progression or death, 0.56; 95% CI, 0.43 to 0.73; P<0.001). The percentage of patients with a complete response or better was 47.6% in the daratumumab group and 24.9% in the control group (P<0.001). A total of 24.2% of the patients in the daratumumab group, as compared with 7.3% of the patients in the control group, had results below the threshold for minimal residual disease (1 tumor cell per 10 5 white cells) (P<0.001). The most common adverse events of grade 3 or 4 were neutropenia (50.0% in the daratumumab group vs. 35.3% in the control group), anemia (11.8% vs. 19.7%), lymphopenia (15.1% vs. 10.7%), and pneumonia (13.7% vs. 7.9%). CONCLUSIONS: Among patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation, the risk of disease progression or death was significantly lower among those who received daratumumab plus lenalidomide and dexamethasone than among those who received lenalidomide and dexamethasone alone. A higher incidence of neutropenia and pneumonia was observed in the daratumumab group. (Funded by Janssen Research and Development; MAIA ClinicalTrials.gov number, NCT02252172.).

AB - BACKGROUND: Lenalidomide plus dexamethasone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation. We sought to determine whether the addition of daratumumab would significantly reduce the risk of disease progression or death in this population.METHODS: We randomly assigned 737 patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation to receive daratumumab plus lenalidomide and dexamethasone (daratumumab group) or lenalidomide and dexamethasone alone (control group). Treatment was to continue until the occurrence of disease progression or unacceptable side effects. The primary end point was progression-free survival.RESULTS: At a median follow-up of 28.0 months, disease progression or death had occurred in 240 patients (97 of 368 patients [26.4%] in the daratumumab group and 143 of 369 patients [38.8%] in the control group). The estimated percentage of patients who were alive without disease progression at 30 months was 70.6% (95% confidence interval [CI], 65.0 to 75.4) in the daratumumab group and 55.6% (95% CI, 49.5 to 61.3) in the control group (hazard ratio for disease progression or death, 0.56; 95% CI, 0.43 to 0.73; P<0.001). The percentage of patients with a complete response or better was 47.6% in the daratumumab group and 24.9% in the control group (P<0.001). A total of 24.2% of the patients in the daratumumab group, as compared with 7.3% of the patients in the control group, had results below the threshold for minimal residual disease (1 tumor cell per 10 5 white cells) (P<0.001). The most common adverse events of grade 3 or 4 were neutropenia (50.0% in the daratumumab group vs. 35.3% in the control group), anemia (11.8% vs. 19.7%), lymphopenia (15.1% vs. 10.7%), and pneumonia (13.7% vs. 7.9%). CONCLUSIONS: Among patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation, the risk of disease progression or death was significantly lower among those who received daratumumab plus lenalidomide and dexamethasone than among those who received lenalidomide and dexamethasone alone. A higher incidence of neutropenia and pneumonia was observed in the daratumumab group. (Funded by Janssen Research and Development; MAIA ClinicalTrials.gov number, NCT02252172.).

KW - Aged

KW - Aged, 80 and over

KW - Antibodies, Monoclonal/administration & dosage

KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects

KW - Dexamethasone/administration & dosage

KW - Female

KW - Humans

KW - Lenalidomide/administration & dosage

KW - Male

KW - Middle Aged

KW - Multiple Myeloma/drug therapy

KW - Neutropenia/chemically induced

KW - Progression-Free Survival

U2 - 10.1056/NEJMoa1817249

DO - 10.1056/NEJMoa1817249

M3 - Journal article

VL - 380

SP - 2104

EP - 2115

JO - The New England Journal of Medicine

JF - The New England Journal of Medicine

SN - 0028-4793

IS - 22

ER -