Literature Scan
Lenalidomide Maintenance Therapy Related to More Secondary Primary Malignancies in Older Adults
Results from the Myeloma XI trial presented at the 2016 ASH Annual Meeting supported the use of lenalidomide as maintenance therapy for patients with newly diagnosed , symptomatic multiple myeloma ( MM ), as it extended progression-free survival without significant toxicity increases . However , in a new analysis from the trial , published in the Blood Cancer Journal , John R . Jones , MD , from the Institute of Cancer Research and the Royal Marsden National Health Service Foundation Trust in London , United Kingdom , and co-authors found that patients receiving lenalidomide maintenance had a significantly higher risk of developing secondary primary malignancies ( SPM ), compared with patients in the observation arm of the study ( p = 0.011 ). The association was even stronger for older patients .
The randomized , multicenter , open-label , phase III Myeloma XI study involved 2,732 patients and compared thalidomide , lenalidomide , and bortezomib induction combinations , followed by lenalidomide with or without vorinostat as maintenance therapy . 1,509 patients were transplanteligible ( median age = 61 years ; range = 28-75 years ) and 1,223 were transplantineligible ( median age = 74 years ; range = 51-89 years ).
Patients were randomized 1:1 to receive induction with a combination regiment of cyclophosphamide and dexamethasone , with either thalidomide or lenalidomide , and dexamethasone . A total of 1,362 patients were then randomized to receive maintenance therapy with single-agent lenalidomide ( n = 527 ), lenalidomide plus vorinostat ( n = 305 ), or observation only ( n = 530 ).
Over a median follow-up of 34.3 months in the lenalidomide group and 24.2 months in the observation group , 104 SPMs in 96 patients were observed : 40 SPMs in 35 transplanteligible patients and 64 SPMs in 61 transplant-ineligible patients .
Thirteen of the SPMs were hematologic ( 0.48 % incidence rate ), including : six cases of myelodysplastic syndromes , three cases of acute myeloid leukemia , two cases of non-Hodgkin lymphoma , one case of Hodgkin lymphoma , and one case of chronic myeloid leukemia . Of the remaining cases , 55 were solid tumors and 36 were non-melanoma skin cancer .
The cumulative incidence of SPM was 0.7 percent ( 95 % CI 0.4-1.0 ) at one year , increasing to 2.3 percent
22 ASH Clinical News
Indication and Important Safety Information
Indication
• VENCLEXTA is indicated for the treatment of patients with chronic lymphocytic leukemia ( CLL ) with 17p deletion , as detected by an FDA-approved test , who have received at least one prior therapy . a
• This indication is approved under accelerated approval based on overall response rate . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial .
Important Safety Information Contraindication
• Concomitant use of VENCLEXTA with strong CYP3A inhibitors at initiation and during ramp-up phase is contraindicated .
Tumor Lysis Syndrome
• Tumor lysis syndrome ( TLS ), including fatal events and renal failure requiring dialysis , has occurred in previously treated CLL patients with high tumor burden treated with VENCLEXTA .
• VENCLEXTA poses a risk for TLS in the initial 5-week ramp-up phase . Changes in blood chemistries consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of VENCLEXTA and at each dose increase .
• Patients should be assessed for TLS risk , including evaluation of tumor burden and comorbidities , and should receive appropriate
VENCLEXTA™ is a trademark of AbbVie , Inc .
( 95 % CI 1.6-2.7 ) at two years . Overall SPM incidence was highest at three years , at 3.8 percent ( 95 % CI 2.9-4.6 ), and SPMs were observed more frequently in transplantineligible patients ( 5.2 % vs . 2.7 %). Among patients exposed to lenalidomide at any time , the researchers observed 73 SPMs . Patients on lenalidomide maintenance had a significantly higher three-year SPM incidence , compared with patients in the observation-only cohort : 8.9 percent versus 4.0 percent ( p = 0.011 ), for a hazard
For CLL patients with 17p deletion who have received at least one prior therapy ...
AIM
prophylaxis for TLS , including hydration and antihyperuricemics . Reduced renal function ( CrCl < 80 mL / min ) further increases the risk . Monitor blood chemistries and manage abnormalities promptly . Interrupt dosing if needed . Employ more intensive measures ( IV hydration , frequent monitoring , hospitalization ) as overall risk increases .
• Concomitant use of VENCLEXTA with strong or moderate CYP3A inhibitors and P-gp inhibitors may increase the risk of TLS at initiation and during the ramp-up phase , and may require dose adjustment due to increases in VENCLEXTA exposure .
Neutropenia
• Grade 3 or 4 neutropenia occurred in 41 % ( 98 / 240 ) of patients treated with VENCLEXTA . Monitor complete blood counts throughout treatment . Interrupt dosing or reduce dose for severe neutropenia . Consider supportive measures including antimicrobials for signs of infection and use of growth factors ( e . g ., G-CSF ).
Immunization
• Do not administer live attenuated vaccines prior to , during , or after treatment with VENCLEXTA until B-cell recovery . Advise patients that vaccinations may be less effective .
Embryo-Fetal Toxicity
• VENCLEXTA may cause embryo-fetal harm when administered
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