Pomalidomide plus low-dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide: comparison of 2 dosing strategies in dual-refractory disease

Lacy, Martha Q.; Allred, Jacob B.; Gertz, Morie A.; Hayman, Suzanne R.; Short, Kristen Detweiler; Buadi, Francis K.; Dispenzieri, Angela; Kumar, Santosh; Greipp, Philip R.; Lust, John A.; Russell, Stephen J.; Dingli, David; Zeldenrust, Steven R.; Fonseca, Rafaël; Bergsagel, P. Leif; Roy, Vivek; Stewart, A. Keith; Laumann, Kristina; Mandrekar, Sumithra J.; Reeder, Craig B.; Rajkumar, S. Vincent; Mıkhael, Joseph

doi:10.1182/blood-2011-04-348896

Cited by 195 publications

(158 citation statements)

References 8 publications

(12 reference statements)

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“…Pomalidomide has significant activity in relapsed refractory myeloma, even in patients failing lenalidomide [114,115]. Response rate in patients refractory to lenalidomide and bortezomib is approximately 30% [116]. MLN-9708 is an oral proteasome inhibitor that has shown promise in both the relapsed refractory setting and in newly diagnosed myeloma.…”

Section: Treatment Of Relapsed Multiple Myelomamentioning

confidence: 99%

Multiple myeloma: 2013 update on diagnosis, risk‐stratification, and management

2013

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Disease overviewMultiple myeloma accounts for approximately 10% of hematologic malignancies.DiagnosisThe diagnosis requires 10% or more clonal plasma cells on bone marrow examination or a biopsy proven plasmacytoma plus evidence of associated end‐organ damage. In addition, the presence of 60% or more clonal plasma cells in the marrow is also considered as myeloma regardless of the presence or absence of end‐organ damage.Risk stratificationIn the absence of concurrent trisomies, patients with 17p deletion, t(14;16), and t(14;20) are considered to have high‐risk myeloma. Patients with t(4;14) translocation are considered intermediate‐risk. All others are considered as standard‐risk.Risk‐adapted initial therapyStandard‐risk patients can be treated with lenalidomide plus low‐dose dexamethasone (Rd), or a bortezomib‐containing triplet such as bortezomib, cyclophosphamide, dexamethasone (VCD). Intermediate‐risk and high‐risk patients require a bortezomib‐based triplet regimen. In eligible patients, initial therapy is given for approximately 4 months followed by autologous stem cell transplantation (ASCT). Standard‐risk patients can opt for delayed ASCT if stem cells can be cryopreserved. In patients are not candidates for transplant, initial therapy is given for approximately 12–18 months.Maintenance therapyAfter initial therapy, lenalidomide maintenance is considered for standard‐risk patients who are not in very good partial response or better, while maintenance with a bortezomib‐based regimen should be considered in pateints with intermediate or high‐risk myeloma.Management of refractory diseasePatients with indolent relapse can be treated first with two‐drug or three‐drug combinations. Patients with more aggressive relapse often require therapy with a combination of multiple active agents. Am. J. Hematol. 88:225–235, 2013. © 2013 Wiley Periodicals, Inc.

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Section: Treatment Of Relapsed Multiple Myelomamentioning

confidence: 99%

Multiple myeloma: 2013 update on diagnosis, risk‐stratification, and management

2013

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“…1 H SCs are a rare population of pluripotent cells that can self-renew and produce various types of cells of the blood lineage. Under steady physiologic conditions, the most primitive HSCs are in a quiescent state and reside in the BM niche where they preserve the capacity to self-renew and to continue to produce all types of blood cells throughout a prolonged lifespan.…”

Section: Comment On Yahata Et Al Page 2941mentioning

confidence: 99%

“…9 These promising results provided the basis of the study designed by Lacy et al to evaluate the efficacy of two different doses of pomalidomide in patients with dual refractoriness (defined as progression on therapy or within 2 months of stopping treatment) to lenalidomide and bortezomib. 1 For this purpose, 70 patients who had received a median of 6 prior therapies (range, 2-11) were enrolled in two sequential phase 2 trials of pomalidomide given continuously at a daily dose of either 4 or 2 mg of 28-day cycles along with 40 mg of dexamethasone on days 1, 8, 15, and 22. The rates of at least minimal response in the 4-mg and 2-mg cohorts were 49% and 43%, respectively, including VGPR and PR rates of 28.5% and 26%, respectively.…”

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confidence: 99%

A third-generation IMiD for MM

Cavo

2011

Blood

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“…Eight patients with stable disease also had a dose increase to 4 mg/day, and one went on to a PR. Subsequent studies have focused on the bortezomib-and lenalidomide-refractory population, and have found that the pomalidomide dose can be escalated to 4 mg daily, when given on a schedule of 21 out of 28 days, with potentially better tolerability than the continuous schedule Lacy et al 2010b;Richardson et al 2010b]. Preliminary results so far have confirmed a PR or better rates between 26% and 42% in this difficult-to-treat population (Table 2), with randomized phase 2 studies comparing the two schedules, and exploring the benefit of dexamethasone, currently ongoing (ClinicalTrials.gov identifiers: NCT01053949 and NCT00833833).…”

Section: Immunomodulatory Drugsmentioning

confidence: 99%

Experimental approaches in the treatment of multiple myeloma

Cohen

2011

Therapeutic Advances in Hematology

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Myeloma therapy has undergone significant advances in recent years resulting in a marked improvement in survival. Knowledge of the active pathways involved in myeloma pathogenesis has led to the discovery of novel agents and greatly expanded the potential armamentarium available for treatment. This better understanding of the disease and resistance mechanisms has resulted in new agent classes that are being evaluated in preclinical and early clinical studies. In addition, dosing for existing agents is being optimized, and they are being given in new combinations. In this article, we review experimental agents that are showing promise in multiple myeloma treatment. New biological agents in clinical trials hold the promise of efficacy through novel mechanisms of action, with a significant reduction of dose-limiting toxicities compared with classic cytotoxic chemotherapeutics. Secondgeneration proteasome inhibitors and immunomodulatory agents are furthest along in clinical development, and histone deacetylase inhibitors, heat shock protein 90 inhibitors, Akt inhibitors and monoclonal antibodies are some of the other agents entering later-phase clinical trials. We also review developments in targeting the myeloma stem cell as an exciting new treatment direction.

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Pomalidomide plus low-dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide: comparison of 2 dosing strategies in dual-refractory disease

Cited by 195 publications

References 8 publications

Multiple myeloma: 2013 update on diagnosis, risk‐stratification, and management

Multiple myeloma: 2013 update on diagnosis, risk‐stratification, and management

A third-generation IMiD for MM

Experimental approaches in the treatment of multiple myeloma

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