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Lenalidomide induction and maintenance in MM
Table 3. Adverse events according to induction regimen (safety popu- lation*).
While three-drug induction regimens are generally more effective than two-drug regimens, they may also be more toxic.10,11 In the Myeloma XI trial, the safety results for CRD and CTD were consistent with the known safety profiles of these agents. Notably, rates of peripheral neu- ropathy were lower with CRD than with CTD. An impor- tant safety concern with lenalidomide treatment in patients with newly diagnosed multiple myeloma is the risk of SPM.43 In this population of transplant-eligible patients, the overall 3-year cumulative incidence of inva- sive SPM was low (2.2%; 95% CI: 1.5-3.0) and the type of induction therapy used did not appear to affect the SPM incidence rate. Safety results for lenalidomide mainte- nance compared to observation, including SPM incidence, have been previously published.23,24 Despite the risks asso- ciated with continued active therapy, registry data suggest that health-related quality of life of patients receiving lenalidomide maintenance is similar to that of patients receiving no maintenance.45
In summary, induction therapy with CRD improved PFS and OS compared with CTD in transplant-eligible patients with newly diagnosed multiple myeloma. The best results were achieved when patients received both lenalidomide-based induction therapy and lenalidomide maintenance.
Disclosures
GHJ has received honoraria from and provided consultancy and speakers bureau services for Roche, Amgen, Janssen, and Merck Sharp and Dohme; and has received honoraria, travel support and research funding from and provided consultancy and speakers bureau services for Celgene Corporation and Takeda. FED reports consultancy for and honoraria from Amgen, AbbVie, Takeda, Janssen and Roche; and consultancy for and honoraria and research funding from Celgene Corporation. CP reports con- sultancy for and travel support from Amgen and Takeda Oncology; honoraria and travel support from Janssen; and con- sultancy for and honoraria and research funding from Celgene Corporation. DAC, AS, CC and AW have received research funding from Celgene Corporation, Amgen, Merck Sharp and Dohme. JRJ has received honoraria and research funding from Celgene Corporation. BK reports consultancy and speakers bureau services for and travel support from Celgene Corporation, Takeda, and Janssen. MG has received travel support and research funding from and participated in speakers bureau for Janssen; has received travel support from Takeda; and travel support and research funding from Novartis. CDW has received honoraria and travel support from and participated in speakers bureau for Takeda, Janssen and Celgene Corporation; has received honoraria from Novartis; and has participated in speak- ers bureau for and received honoraria from Novartis. KK has received travel support and research funding from Celgene Corporation and Janssen. JL has provided consultancy services for Janssen; received travel support from Novartis; honoraria and travel support from Takeda; has acted as a consultant for and received travel support from Bristol-Myers Squibb; and reports consulting for and honoraria and travel support from Celgene Corporation. DA and NHR have nothing to disclose. SS reports travel support from Celgene Corporation and Janssen; speaker services for Pfizer; and meeting sponsorship from AbbVie. MWJ reports consultancy for and honoraria, travel support, and research funding from Janssen; consultancy for and honoraria and research funding from Celgene Corporation; consultancy for and honoraria from Novartis; and consultancy for and honoraria and travel support from Takeda and Amgen GC repports con-
Grade ≥3 AE, n (%) Neutropenia
Anemia
Thrombocytopenia
Diarrhea
Constipation
Peripheral sensory neuropathy
Peripheral motor neuropathy
AEs of interest (any grade), n (%)
Peripheral sensory neuropathy
Peripheral motor neuropathy
Deep vein thrombosis
Pulmonary embolism
Other thrombosis/embolism
CRD (n=1,010)
225 (22.3)
97 (9.6)
46 (4.5)
26 (2.6)
8 (0.8)
6 (0.6)
5 (0.5)
CRD (n=1,010)
251 (24.9)
87 (8.6)
58 (5.7)
32 (3.2)
8 (0.8)
CTD (n=1,004)
117 (11.7)
67 (6.7)
17 (1.7)
10 (1.0)
19 (1.9)
15 (1.5)
14 (1.4)
CTD (n=1,004)
452 (45.0)
163 (16.2)
48 (4.8)
49 (4.9)
11 (1.1)
*The safety population included all randomly assigned patients who received one or more doses of the induction or maintenance regimen. AE: adverse event; CRD: cyclophosphamide, lenalidomide, and dexamethasone; CTD: cyclophosphamide, thalidomide, and dexamethasone.
modifications and so is difficult to explain. The PFS differ- ence is small, not statistically significant and may have occurred by chance. In the analysis of OS the reverse pat- tern was seen with patients receiving CRD and observa- tion having an apparent improved OS compared to those receiving CTD and observation.
The results of Myeloma XI are likely to reflect the true impact of the CRD combination in clinical practice because of the limited exclusion criteria for the study pop- ulation. Notably, there were no age restrictions for the intensive pathway, allowing older but fit patients to undergo ASCT. The median age in this group was 61 years, and patients up to the age of 75 years were includ- ed. In contrast, most previous studies of ASCT have excluded patients aged over 65 or 70 years. Evidence sug- gests that fit patients aged >65 years can benefit from ASCT, especially when combined with regimens contain- ing novel agents.3,39,40 Our approach may also explain the relatively lower proportion of patients proceeding to ASCT in this study than in other studies of induction ther- apy which are usually limited only to patients under the age of 65. The most common reason for patients not pro- ceeding to stem-cell transplant was given as “patient not fit/clinician’s decision” suggesting that clinicians may have initially entered patients in the transplant-eligible path- way of the study as a ‘trial of fitness’ so as not to limit their options prior to withdrawing the patient nearer the time of transplantation.
In addition, the proportion of patients with ISS stage III disease (24%) in the present study was slightly higher than that in some recent studies of induction therapy.9,10,31,35 Cytogenetic abnormalities, such as t(4;14), t(14;16), and del(17p), are important prognostic markers, and should therefore be investigated in all patients with multiple myeloma according to the International Myeloma Working Group molecular classification.41 Although cyto- genetic data were only available for 41% of patients in our study, this percentage is comparable to that in other trials of patients with newly diagnosed multiple myeloma.42
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