Adverse event management in patients with relapsed and refractory multiple myeloma taking pomalidomide plus low‐dose dexamethasone: A pooled analysis

Moreau, Philippe; Dimopoulos, Meletios Α.; Richardson, Paul G.; Siegel, David S.; Cavo, Michèle; Corradini, Paolo; Weisel, Katja; Delforge, Michel; O’Gorman, Peter; Song, Kevin; Chen, Christine; Bahlis, Nizar J.; Oriol, Albert; Hansson, Markus; Kaiser, Martin; Anttila, Pekka; Raymakers, Reinier; João, Cristina; Cook, Gordon; Sternås, Lars; Biyukov, Tsvetan; Slaughter, Ana; Hong, Kevin; Herring, Jennifer; Yu, Xin; Zaki, Mohamed H.; Miguel, Jesús F. San

doi:10.1111/ejh.12903

Cited by 22 publications

(17 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The 6% occurrence of deep vein thrombosis remains low compared with lenalidomide and thalidomide . Except for peripheral neuropathy, our safety data are in line with those reported in clinical trials, and have the major strength of adding additional information over a longer period (median follow‐up longer than 18 months) with a “real‐world” use. The elevated percentages of peripheral neuropathy in our cohort (any grade, 29%; grade ≥3, 6%) are probably explained by the fact that we did not restrict the use of pomalidomide in patients with grade <2 peripheral neuropathy (14% of our patients).…”

Section: Discussionsupporting

confidence: 78%

“…pomalidomide-dexamethasone regimen. Except for peripheral neuropathy, our safety data are in line with those reported in clinical trials,6,[16][17][18]20,21 and have the major strength of adding additional information over a longer period (median follow-up longer than 18 months) with a "realworld" use. A total of 34 (54%) patients experienced at least 1 grade ≥3 AE, mainly hematologic or infectious.…”

supporting

confidence: 75%

See 1 more Smart Citation

Efficacy, safety, and cost of pomalidomide in relapsed and refractory multiple myeloma

Guéneau

Chrétien

Cransac-Miet³

et al. 2018

European J of Haematology

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 78%

supporting

confidence: 75%

Efficacy, safety, and cost of pomalidomide in relapsed and refractory multiple myeloma

Guéneau

Chrétien

Cransac-Miet³

et al. 2018

European J of Haematology

View full text Add to dashboard Cite

show abstract

“…The most common adverse events (AEs; all grades) related to 300 mg avapritinib in ≥35% of patients were nausea, fatigue, and anemia [26]. Supportive care and flexible dosing strategies (including dose interruptions and/or reductions), which are common strategies for managing AEs associated with multi-targeted TKIs [28][29][30][31][32], were used to manage the AEs seen with avapritinib in the NAVIGATOR phase I study.…”

Section: Introductionmentioning

confidence: 99%

Optimal Avapritinib Treatment Strategies for Patients with Metastatic or Unresectable Gastrointestinal Stromal Tumors

et al. 2021

View full text Add to dashboard Cite

Background Avapritinib, a novel inhibitor of KIT/PDGFRA, is approved in the U.S. for the treatment of adults with PDGFRA exon 18‐mutant unresectable or metastatic gastrointestinal stromal tumors (U/M GISTs). We assessed the safety of avapritinib and provide evidence‐based guidance on management of avapritinib‐associated adverse events (AEs), including cognitive effects and intracranial bleeding. Materials and Methods We performed a post hoc analysis of data from a two‐part, single‐arm dose escalation/expansion phase I study (NAVIGATOR; NCT02508532) in patients with U/M GISTs treated with oral avapritinib 30–600 mg once daily. The primary endpoints were safety and tolerability; the impact of dose modification (interruption and/or reduction) on progression‐free survival (PFS) was a secondary endpoint. Efficacy analyses were limited to patients who started avapritinib at 300 mg (approved dose). Results Of 250 patients enrolled in the study, 74.0% presented with KIT mutation and 24.8% presented with PDGFRA exon 18‐mutation; 66.8% started avapritinib at 300 mg. The most common treatment‐related AEs (any grade) were nausea (59.2%), fatigue (50.0%), periorbital edema (42.0%), anemia (39.2%), diarrhea (36.0%), vomiting (36.0%), and increased lacrimation (30.8%). No treatment‐related deaths occurred. Among 167 patients starting on 300 mg avapritinib, all‐cause cognitive effects rate (grade 1–2) was 37.0% in all patients and 52.0% in patients ≥65 years. Cognitive effects improved to a lower grade more quickly with dose modification (1.3–3.1 weeks) than without (4.9–7.6 weeks). Median PFS was 11.4 months with dose modification and 7.2 months without. Conclusion Tolerability‐guided dose modification of avapritinib is an effective strategy for managing AEs in patients with GISTs. Implications for Practice Early recognition of adverse events and tailored dose modification appear to be effective approaches for managing treatment‐related adverse events and maintaining patients on avapritinib. Dose reduction does not appear to result in reduced efficacy. Patients' cognitive function should be assessed at baseline and monitored carefully throughout treatment with avapritinib for the onset of cognitive adverse events. Dose interruption is recommended at the first sign of any cognitive effect, including grade 1 events.

show abstract

“…Based on the results of the phase 2 trial (MM-002) (8) and MM-003, POM was approved in the United States, European Union and other countries in 2013. A recent phase 3b trial (MM-010) proved the safety and efficacy of POM in a large population of RRMM patients refractory to LEN and BOR treatment (9,10).…”

Section: Introductionmentioning

confidence: 99%

Tolerability and safety of real‑world use of pomalidomide in patients with relapsed/refractory multiple myeloma

et al. 2018

View full text Add to dashboard Cite

Pomalidomide (POM) is a second-generation immunomodulatory agent with proven efficacy in patients with relapsed/refractory multiple myeloma (RRMM) proven to be refractory to previous treatment with lenalidomide (LEN) and bortezomib. We herein conducted a retrospective analysis of 14 RRMM patients receiving POM to determine its tolerability and safety in the clinical setting. The median age of the patients was 72 years (range, 58-84 years), and 85.7% of the patients were aged >70 years. The most frequent treatment dose was 3 mg/day. POM dose reductions were required in 54.5% (6/11) of the patients. The patient data were compared among three age groups (<70, 70-75 and >75 years) and there was only significant difference in daily POM treatment dose. The tolerability of POM must be confirmed, particularly in elderly patients. Dose reduction from 4 to 3 mg occurred during the second cycle in 83.3% (5/6) of the patients. It is important to determine the tolerability of POM in the early phases of treatment. The most frequently reported grade 3/4 hematological adverse events were neutropenia (64.3%), anemia (64.3%) and thrombocytopenia (57.1%). Although the median number of treatment cycles was 4 (range, 1-13), 21.4% (3/14) of the patients with a performance status (PS) of 3 were administered only 1 treatment cycle. The tolerability of POM was low among patients with poor PS and an aggressive treatment introduction should be avoided. However, 21.4% (3/14) of the patients were able to continue treatment for >1 year and some patients received long-term therapy. POM does not require dose modification for renal function, and multiple capsule doses are available, which is an advantage of POM compared with LEN. POM may be administered to late-stage RRMM patients in a real-world clinical setting, but elderly patients or those with poor PS must be treated with caution. In this manner, the treatment options for RRMM patients may be expanded by assessing the tolerability and safety of POM.

show abstract

Adverse event management in patients with relapsed and refractory multiple myeloma taking pomalidomide plus low‐dose dexamethasone: A pooled analysis

Abstract: Pomalidomide plus low-dose dexamethasone showed an acceptable safety profile, and AEs were well managed according to study protocols and established guidelines.

Cited by 22 publications

References 27 publications

Efficacy, safety, and cost of pomalidomide in relapsed and refractory multiple myeloma

Efficacy, safety, and cost of pomalidomide in relapsed and refractory multiple myeloma

Optimal Avapritinib Treatment Strategies for Patients with Metastatic or Unresectable Gastrointestinal Stromal Tumors

Tolerability and safety of real‑world use of pomalidomide in patients with relapsed/refractory multiple myeloma

Contact Info

Product

Resources

About