Pomalidomide, bortezomib, and dexamethasone for patients with relapsed lenalidomide-refractory multiple myeloma

Jonas Paludo, Joseph R Mikhael, Betsy R. Laplant, Alese E. Halvorson, Shaji K Kumar, Morie Gertz, Suzanne R. Hayman, Francis K. Buadi, Angela Dispenzieri, John A. Lust, Prashant Kapoor, Nelson Leung, Stephen J Russell, David M Dingli, Ronald S. Go, Yi Lin, Wilson Gonsalves, Rafael Fonseca, Peter Leif Bergsagel, Vivek RoyTaimur Sher, Asher A Chanan Khan, Sikander Ailawadhi, Alexander Keith Stewart, Craig B. Reeder, Paul G. Richardson, S Vincent Rajkumar, Martha Lacy

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

This phase 1/2 trial evaluated the maximum tolerated doses, safety, and efficacy of pomalidomide, bortezomib, and dexamethasone (PVD) combination in patients with relapsed lenalidomide-refractory multiple myeloma (MM). In phase 1, dose level 1 consisted of pomalidomide (4 mg by mouth on days 1 to 21), IV or subcutaneous bortezomib (1.0 mg/m2 on days 1, 8, 15, and 22), and dexamethasone (40 mg by mouth on days 1, 8, 15, and 22) given every 28 days. Bortezomib was increased to 1.3 mg/m2 for dose level 2 and adopted in the phase 2 expansion cohort. We describe the results of 50 patients. Objective response rate was 86% (95% confidence interval [CI], 73-94) among all evaluable patients (stringent complete response, 12%; complete response, 10%; very good partial response, 28%; and partial response, 36%) and 100% among high-risk patients. Within a median follow-up of 42 months, 20% remain progression free, 66% are alive, and 4% remain on treatment. Median progression-free survival was 13.7 months (95% CI, 9.6-17.7). The most common toxicities were neutropenia (96%), leukopenia (84%), thrombocytopenia (82%), anemia (74%), and fatigue (72%); however, the majority of these were grade 1 or 2. The most common grade ≥3 toxicities included neutropenia (70%), leukopenia (36%), and lymphopenia (20%). Deep vein thrombosis occurred in 5 patients. In conclusion, PVD is a highly effective combination in lenalidomide-refractory MM patients. Weekly administration of bortezomib enhanced tolerability and convenience. Toxicities are manageable, mostly consisting of mild cytopenias with no significant neuropathy. This trial was registered at www.clinicaltrials.gov as #NCT01212952.

Original languageEnglish (US)
Pages (from-to)1198-1204
Number of pages7
JournalBlood
Volume130
Issue number10
DOIs
StatePublished - Sep 7 2017

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Multiple Myeloma
Refractory materials
Dexamethasone
Toxicity
Physical vapor deposition
Leukopenia
Neutropenia
Mouth
Confidence Intervals
Lymphopenia
Maximum Tolerated Dose
Fatigue of materials
Venous Thrombosis
Thrombocytopenia
Disease-Free Survival
Fatigue
lenalidomide
Bortezomib
pomalidomide
Anemia

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Pomalidomide, bortezomib, and dexamethasone for patients with relapsed lenalidomide-refractory multiple myeloma. / Paludo, Jonas; Mikhael, Joseph R; Laplant, Betsy R.; Halvorson, Alese E.; Kumar, Shaji K; Gertz, Morie; Hayman, Suzanne R.; Buadi, Francis K.; Dispenzieri, Angela; Lust, John A.; Kapoor, Prashant; Leung, Nelson; Russell, Stephen J; Dingli, David M; Go, Ronald S.; Lin, Yi; Gonsalves, Wilson; Fonseca, Rafael; Bergsagel, Peter Leif; Roy, Vivek; Sher, Taimur; Chanan Khan, Asher A; Ailawadhi, Sikander; Stewart, Alexander Keith; Reeder, Craig B.; Richardson, Paul G.; Rajkumar, S Vincent; Lacy, Martha.

In: Blood, Vol. 130, No. 10, 07.09.2017, p. 1198-1204.

Research output: Contribution to journalArticle

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abstract = "This phase 1/2 trial evaluated the maximum tolerated doses, safety, and efficacy of pomalidomide, bortezomib, and dexamethasone (PVD) combination in patients with relapsed lenalidomide-refractory multiple myeloma (MM). In phase 1, dose level 1 consisted of pomalidomide (4 mg by mouth on days 1 to 21), IV or subcutaneous bortezomib (1.0 mg/m2 on days 1, 8, 15, and 22), and dexamethasone (40 mg by mouth on days 1, 8, 15, and 22) given every 28 days. Bortezomib was increased to 1.3 mg/m2 for dose level 2 and adopted in the phase 2 expansion cohort. We describe the results of 50 patients. Objective response rate was 86{\%} (95{\%} confidence interval [CI], 73-94) among all evaluable patients (stringent complete response, 12{\%}; complete response, 10{\%}; very good partial response, 28{\%}; and partial response, 36{\%}) and 100{\%} among high-risk patients. Within a median follow-up of 42 months, 20{\%} remain progression free, 66{\%} are alive, and 4{\%} remain on treatment. Median progression-free survival was 13.7 months (95{\%} CI, 9.6-17.7). The most common toxicities were neutropenia (96{\%}), leukopenia (84{\%}), thrombocytopenia (82{\%}), anemia (74{\%}), and fatigue (72{\%}); however, the majority of these were grade 1 or 2. The most common grade ≥3 toxicities included neutropenia (70{\%}), leukopenia (36{\%}), and lymphopenia (20{\%}). Deep vein thrombosis occurred in 5 patients. In conclusion, PVD is a highly effective combination in lenalidomide-refractory MM patients. Weekly administration of bortezomib enhanced tolerability and convenience. Toxicities are manageable, mostly consisting of mild cytopenias with no significant neuropathy. This trial was registered at www.clinicaltrials.gov as #NCT01212952.",
author = "Jonas Paludo and Mikhael, {Joseph R} and Laplant, {Betsy R.} and Halvorson, {Alese E.} and Kumar, {Shaji K} and Morie Gertz and Hayman, {Suzanne R.} and Buadi, {Francis K.} and Angela Dispenzieri and Lust, {John A.} and Prashant Kapoor and Nelson Leung and Russell, {Stephen J} and Dingli, {David M} and Go, {Ronald S.} and Yi Lin and Wilson Gonsalves and Rafael Fonseca and Bergsagel, {Peter Leif} and Vivek Roy and Taimur Sher and {Chanan Khan}, {Asher A} and Sikander Ailawadhi and Stewart, {Alexander Keith} and Reeder, {Craig B.} and Richardson, {Paul G.} and Rajkumar, {S Vincent} and Martha Lacy",
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AU - Paludo, Jonas

AU - Mikhael, Joseph R

AU - Laplant, Betsy R.

AU - Halvorson, Alese E.

AU - Kumar, Shaji K

AU - Gertz, Morie

AU - Hayman, Suzanne R.

AU - Buadi, Francis K.

AU - Dispenzieri, Angela

AU - Lust, John A.

AU - Kapoor, Prashant

AU - Leung, Nelson

AU - Russell, Stephen J

AU - Dingli, David M

AU - Go, Ronald S.

AU - Lin, Yi

AU - Gonsalves, Wilson

AU - Fonseca, Rafael

AU - Bergsagel, Peter Leif

AU - Roy, Vivek

AU - Sher, Taimur

AU - Chanan Khan, Asher A

AU - Ailawadhi, Sikander

AU - Stewart, Alexander Keith

AU - Reeder, Craig B.

AU - Richardson, Paul G.

AU - Rajkumar, S Vincent

AU - Lacy, Martha

PY - 2017/9/7

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N2 - This phase 1/2 trial evaluated the maximum tolerated doses, safety, and efficacy of pomalidomide, bortezomib, and dexamethasone (PVD) combination in patients with relapsed lenalidomide-refractory multiple myeloma (MM). In phase 1, dose level 1 consisted of pomalidomide (4 mg by mouth on days 1 to 21), IV or subcutaneous bortezomib (1.0 mg/m2 on days 1, 8, 15, and 22), and dexamethasone (40 mg by mouth on days 1, 8, 15, and 22) given every 28 days. Bortezomib was increased to 1.3 mg/m2 for dose level 2 and adopted in the phase 2 expansion cohort. We describe the results of 50 patients. Objective response rate was 86% (95% confidence interval [CI], 73-94) among all evaluable patients (stringent complete response, 12%; complete response, 10%; very good partial response, 28%; and partial response, 36%) and 100% among high-risk patients. Within a median follow-up of 42 months, 20% remain progression free, 66% are alive, and 4% remain on treatment. Median progression-free survival was 13.7 months (95% CI, 9.6-17.7). The most common toxicities were neutropenia (96%), leukopenia (84%), thrombocytopenia (82%), anemia (74%), and fatigue (72%); however, the majority of these were grade 1 or 2. The most common grade ≥3 toxicities included neutropenia (70%), leukopenia (36%), and lymphopenia (20%). Deep vein thrombosis occurred in 5 patients. In conclusion, PVD is a highly effective combination in lenalidomide-refractory MM patients. Weekly administration of bortezomib enhanced tolerability and convenience. Toxicities are manageable, mostly consisting of mild cytopenias with no significant neuropathy. This trial was registered at www.clinicaltrials.gov as #NCT01212952.

AB - This phase 1/2 trial evaluated the maximum tolerated doses, safety, and efficacy of pomalidomide, bortezomib, and dexamethasone (PVD) combination in patients with relapsed lenalidomide-refractory multiple myeloma (MM). In phase 1, dose level 1 consisted of pomalidomide (4 mg by mouth on days 1 to 21), IV or subcutaneous bortezomib (1.0 mg/m2 on days 1, 8, 15, and 22), and dexamethasone (40 mg by mouth on days 1, 8, 15, and 22) given every 28 days. Bortezomib was increased to 1.3 mg/m2 for dose level 2 and adopted in the phase 2 expansion cohort. We describe the results of 50 patients. Objective response rate was 86% (95% confidence interval [CI], 73-94) among all evaluable patients (stringent complete response, 12%; complete response, 10%; very good partial response, 28%; and partial response, 36%) and 100% among high-risk patients. Within a median follow-up of 42 months, 20% remain progression free, 66% are alive, and 4% remain on treatment. Median progression-free survival was 13.7 months (95% CI, 9.6-17.7). The most common toxicities were neutropenia (96%), leukopenia (84%), thrombocytopenia (82%), anemia (74%), and fatigue (72%); however, the majority of these were grade 1 or 2. The most common grade ≥3 toxicities included neutropenia (70%), leukopenia (36%), and lymphopenia (20%). Deep vein thrombosis occurred in 5 patients. In conclusion, PVD is a highly effective combination in lenalidomide-refractory MM patients. Weekly administration of bortezomib enhanced tolerability and convenience. Toxicities are manageable, mostly consisting of mild cytopenias with no significant neuropathy. This trial was registered at www.clinicaltrials.gov as #NCT01212952.

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