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 language | English (US) |
|---|---|
| Pages (from-to) | 1198-1204 |
| Number of pages | 7 |
| Journal | Blood |
| Volume | 130 |
| Issue number | 10 |
| DOIs | |
| State | Published - Sep 7 2017 |
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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 journal › Article
}
TY - JOUR
T1 - Pomalidomide, bortezomib, and dexamethasone for patients with relapsed lenalidomide-refractory multiple myeloma
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
Y1 - 2017/9/7
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.
UR - http://www.scopus.com/inward/record.url?scp=85029319594&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85029319594&partnerID=8YFLogxK
U2 - 10.1182/blood-2017-05-782961
DO - 10.1182/blood-2017-05-782961
M3 - Article
C2 - 28684537
AN - SCOPUS:85029319594
VL - 130
SP - 1198
EP - 1204
JO - Blood
JF - Blood
SN - 0006-4971
IS - 10
ER -