Limits...
Lenalidomide before and after Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma.

Tuchman SA, Chao NJ, Gasparetto CG - Adv Hematol (2012)

Bottom Line: In the non-transplant and relapsed/refractory settings, lenalidomide clearly benefits patients in terms of virtually all meaningful outcomes including overall survival.That said, relatively preliminary efficacy data describing lenalidomide as a component of ASCT-based treatment approaches to MM are indeed promising, and consequently lenalidomide's role in ASCT-based treatment strategies is growing.In this review we summarize existing data that pertains to lenalidomide in the specific context of ASCT, and we share our thoughts on how our own group applies these data to approach this complex issue clinically.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Oncology and Hematological Malignancies Program, Duke University Medical Center, Durham, NC 27710, USA.

ABSTRACT
Although multiple myeloma remains incurable outside of allogeneic hematopoietic stem cell transplantation, novel agents made available only in the last few decades have nonetheless tremendously improved the landscape of myeloma treatment. Lenalidomide, of the immunomodulatory class of drugs, is one of those novel agents. In the non-transplant and relapsed/refractory settings, lenalidomide clearly benefits patients in terms of virtually all meaningful outcomes including overall survival. Data supporting the usage of lenalidomide as part of treatment approaches incorporating high-dose chemotherapy with autologous stem cell support (ASCT) are less mature as pertains to such long-term outcomes and toxicity, and lenalidomide is not currently approved by regulatory agencies for use in the context of ASCT in either the United States or Europe. That said, relatively preliminary efficacy data describing lenalidomide as a component of ASCT-based treatment approaches to MM are indeed promising, and consequently lenalidomide's role in ASCT-based treatment strategies is growing. In this review we summarize existing data that pertains to lenalidomide in the specific context of ASCT, and we share our thoughts on how our own group applies these data to approach this complex issue clinically.

No MeSH data available.


Related in: MedlinePlus

Reported response rates for lenalidomide-based induction regimens for MM. Rates depicted are those that could be ascertained either directly using reported data or as calculated using reported data. (a) Response rates after four cycles of therapy. Deeper response rates are not displayed due to inconsistent reporting in referenced sources. (b) Best response reached on study. Rates after four cycles could be envisioned as a measure of expected response pre-ASCT, whereas best response rate may represent a regimen's maximum potential, but only after more cycles than a patient would usually be administered as pre-ASCT induction. Data was gleaned from the following sources: RD and Rd [9]; RVD [11]; CRD [12]; BiRD [10]; and RVDDoxil [14].
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3368529&req=5

fig1: Reported response rates for lenalidomide-based induction regimens for MM. Rates depicted are those that could be ascertained either directly using reported data or as calculated using reported data. (a) Response rates after four cycles of therapy. Deeper response rates are not displayed due to inconsistent reporting in referenced sources. (b) Best response reached on study. Rates after four cycles could be envisioned as a measure of expected response pre-ASCT, whereas best response rate may represent a regimen's maximum potential, but only after more cycles than a patient would usually be administered as pre-ASCT induction. Data was gleaned from the following sources: RD and Rd [9]; RVD [11]; CRD [12]; BiRD [10]; and RVDDoxil [14].

Mentions: The ECOG's E4A03 study (n = 445) included both ASCT candidates and noncandidates and was designed with the primary endpoint of testing noninferiority of lenalidomide given with low-dose (weekly) dexamethasone (i.e., the Rd regimen; Table 1) to RD. Patients on RD demonstrated more objective responses than patients taking Rd (overall response rate ORR 81% versus 70%, P = 0.008; Figure 1), but at the price of inferior one-year overall survival (87% one-year overall survival OS for RD versus 96% for Rd, P = 0.0002). Closer inspection reveals that the increased mortality with RD was likely associated with the higher rate of grade 3 or greater venous thromboembolic events, infection, or cardiac complications than Rd and that toxicity occurred primarily in the first four months of therapy. In terms of ASCT, 39.5% of patients in this study attempted ASCT after four cycles of induction, 98% of whom did so successfully. Among ASCT patients, median three-year OS was 92% and similar between the RD and Rd groups. RD and Rd both emerged as clearly effective regimens for pre-ASCT induction. Although the OS one-year benefit to Rd has resulted in the more widespread usage of low-dose dexamethasone than high-dose, for patients going to ASCT, one should recall that the survival benefit with Rd was specifically in patients not going for ASCT [9].


Lenalidomide before and after Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma.

Tuchman SA, Chao NJ, Gasparetto CG - Adv Hematol (2012)

Reported response rates for lenalidomide-based induction regimens for MM. Rates depicted are those that could be ascertained either directly using reported data or as calculated using reported data. (a) Response rates after four cycles of therapy. Deeper response rates are not displayed due to inconsistent reporting in referenced sources. (b) Best response reached on study. Rates after four cycles could be envisioned as a measure of expected response pre-ASCT, whereas best response rate may represent a regimen's maximum potential, but only after more cycles than a patient would usually be administered as pre-ASCT induction. Data was gleaned from the following sources: RD and Rd [9]; RVD [11]; CRD [12]; BiRD [10]; and RVDDoxil [14].
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3368529&req=5

fig1: Reported response rates for lenalidomide-based induction regimens for MM. Rates depicted are those that could be ascertained either directly using reported data or as calculated using reported data. (a) Response rates after four cycles of therapy. Deeper response rates are not displayed due to inconsistent reporting in referenced sources. (b) Best response reached on study. Rates after four cycles could be envisioned as a measure of expected response pre-ASCT, whereas best response rate may represent a regimen's maximum potential, but only after more cycles than a patient would usually be administered as pre-ASCT induction. Data was gleaned from the following sources: RD and Rd [9]; RVD [11]; CRD [12]; BiRD [10]; and RVDDoxil [14].
Mentions: The ECOG's E4A03 study (n = 445) included both ASCT candidates and noncandidates and was designed with the primary endpoint of testing noninferiority of lenalidomide given with low-dose (weekly) dexamethasone (i.e., the Rd regimen; Table 1) to RD. Patients on RD demonstrated more objective responses than patients taking Rd (overall response rate ORR 81% versus 70%, P = 0.008; Figure 1), but at the price of inferior one-year overall survival (87% one-year overall survival OS for RD versus 96% for Rd, P = 0.0002). Closer inspection reveals that the increased mortality with RD was likely associated with the higher rate of grade 3 or greater venous thromboembolic events, infection, or cardiac complications than Rd and that toxicity occurred primarily in the first four months of therapy. In terms of ASCT, 39.5% of patients in this study attempted ASCT after four cycles of induction, 98% of whom did so successfully. Among ASCT patients, median three-year OS was 92% and similar between the RD and Rd groups. RD and Rd both emerged as clearly effective regimens for pre-ASCT induction. Although the OS one-year benefit to Rd has resulted in the more widespread usage of low-dose dexamethasone than high-dose, for patients going to ASCT, one should recall that the survival benefit with Rd was specifically in patients not going for ASCT [9].

Bottom Line: In the non-transplant and relapsed/refractory settings, lenalidomide clearly benefits patients in terms of virtually all meaningful outcomes including overall survival.That said, relatively preliminary efficacy data describing lenalidomide as a component of ASCT-based treatment approaches to MM are indeed promising, and consequently lenalidomide's role in ASCT-based treatment strategies is growing.In this review we summarize existing data that pertains to lenalidomide in the specific context of ASCT, and we share our thoughts on how our own group applies these data to approach this complex issue clinically.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Oncology and Hematological Malignancies Program, Duke University Medical Center, Durham, NC 27710, USA.

ABSTRACT
Although multiple myeloma remains incurable outside of allogeneic hematopoietic stem cell transplantation, novel agents made available only in the last few decades have nonetheless tremendously improved the landscape of myeloma treatment. Lenalidomide, of the immunomodulatory class of drugs, is one of those novel agents. In the non-transplant and relapsed/refractory settings, lenalidomide clearly benefits patients in terms of virtually all meaningful outcomes including overall survival. Data supporting the usage of lenalidomide as part of treatment approaches incorporating high-dose chemotherapy with autologous stem cell support (ASCT) are less mature as pertains to such long-term outcomes and toxicity, and lenalidomide is not currently approved by regulatory agencies for use in the context of ASCT in either the United States or Europe. That said, relatively preliminary efficacy data describing lenalidomide as a component of ASCT-based treatment approaches to MM are indeed promising, and consequently lenalidomide's role in ASCT-based treatment strategies is growing. In this review we summarize existing data that pertains to lenalidomide in the specific context of ASCT, and we share our thoughts on how our own group applies these data to approach this complex issue clinically.

No MeSH data available.


Related in: MedlinePlus