Myeloma Treatment Sequencing
information ,” noted S . Vincent Rajkumar , MD , a hematologist-oncologist at the Mayo Clinic in Rochester , Minnesota , and chair of the Eastern Cooperative Oncology Group Myeloma Committee . “ We have several high-quality trials that have given us better data , but the number of options can be a bit overwhelming .”
A New Diagnosis
Patients with newly diagnosed disease are starting with a clean slate , so to speak . Because they are treatment-naïve , toxicities and adverse events ( AEs ) from previous treatments do not need to be factored into the treatment equation . Of course , any sequence will need to be tailored based on various patient factors . As such , the International Myeloma Working Group created a geriatric assessment tool based on age , comorbidities , cognitive condition , and physical condition that categorizes patients as “ fit ,” “ intermediate ,” or “ frail .” 3
Recently , triplet therapies have become a standard for this patient population because they lead to a greater proportion of patients achieving complete remission , tolerating treatment longer , and having longer progression-free survival ( PFS ). However , the intensity of this treatment regimen precludes some patients from receiving it .
Patients with higher performance status scores who are deemed fit or intermediate can tolerate more aggressive therapy . As the number of therapies increases , the performance status tends to decrease , Dr . Lonial noted , but that decline generally happens much later with newer agents . “ Many people think about sequencing [ individual drugs ] in lieu of combination therapy . What we ’ ve learned in the last few years is that combination therapies are clearly more effective and attack MM from multiple fronts ,” Dr . Lonial said . “ Given that MM can often change or morph and is a genetically complicated disease , hitting it with a single drug , or even a doublet , is almost always going to be a suboptimal approach .”
The triplet combination of lenalidomide , bortezomib , and dexamethasone ( known as RVD ) is the goto firstline treatment in patients with MM who are not candidates for transplant . Dr . Rajkumar confirmed that , at the Mayo Clinic , most non-transplant patients receive RVD as frontline treatment , usually for one year , and then receive maintenance therapy , most commonly with lenalidomide and dexamethasone .
According to results from the Southwest Oncology Group ( SWOG ) S0777 trial , fit and intermediate
36 ASH Clinical News
patients who were treated with RVD had a longer median PFS and overall survival ( OS ), compared with patients treated with lenalidomide and dexamethasone alone ( RD ; 43 months vs . 30 months and 75 months vs . 64 months , respectively ; p = 0.018 ). 4
“ Previous trials compared a new regimen to an old regimen or compared two newer regimens , but did not show a survival benefit ,” Dr . Rajkumar said . “ SWOG was the first to compare modern regimens and show that a triplet is better than the doublet combination .”
Unfortunately , frail patients are likely to experience worse OS with RVD than fit patients ( 57 % vs . 84 %; p = 0.025 ) and are prone to experience more toxicity . In these cases , Dr . Rajkumar said he opts for the older RD sequence .
For patients who have worse performance status scores , Drs . Yee and Raje
IMPORTANT SAFETY INFORMATION
Contraindication : History of hypersensitivity to BOSULIF . Reactions have included anaphylaxis . Anaphylactic shock occurred in less than 0.2 % of treated patients in clinical trials .
Gastrointestinal Toxicity : Diarrhea , nausea , vomiting , and abdominal pain can occur . In the clinical trial , median time to onset for diarrhea was 2 days , median duration was 1 day , and median number of episodes per patient was 3 ( range 1-221 ). Monitor and manage patients using standards of care , including antidiarrheals , antiemetics , and / or fluid replacement . Withhold , dose reduce , or discontinue BOSULIF as necessary .
Myelosuppression : Thrombocytopenia , anemia , and neutropenia can occur . Perform complete blood counts weekly for the first month and then monthly or as clinically indicated . Withhold , dose reduce , or discontinue BOSULIF as necessary .
Hepatic Toxicity : Twenty percent of patients experienced an increase in either ALT or AST . Liver enzyme elevation usually occurs early in treatment . Perform recommend an alternative sequence referred to as “ RVD-lite ,” in which the drugs are administered on a more “ user-friendly schedule ” that includes an extended treatment cycle , a lower dose of lenalidomide , and a modified bortezomib schedule . 5
If at First You Don ’ t Succeed …
These regimens are not likely to be curative , though , and as a result relapse ( or death from MM or other causes ) is almost
BOSULIF is indicated for the treatment of adult patients with chronic , accelerated , or blast phase Philadelphia chromosome – positive ( Ph +) chronic myelogenous leukemia ( CML ) with resistance or intolerance to prior therapy .
In the treatment of adult patients with Ph + CML with resistance or intolerance to prior therapy
Everyone has a distinct profile
Consider your patient . Consider BOSULIF .
( bosutinib )
Bosutinib ( BOSULIF ®) is recommended by the NCCN Clinical Practice Guidelines in Oncology ( NCCN Guidelines ®) as a treatment option for patients with CML in need of 2nd- or later-line TKI therapy . 1
Study design : BOSULIF 500 mg once-daily treatment was studied in a single-arm , Phase 1 / 2 , open-label , multicenter trial ( N = 546 ) in patients with CP , AP , or BP CML in second line ( after imatinib ) or in third line ( after imatinib followed by dasatinib and / or nilotinib ). Of the 546 patients enrolled , 73 % were imatinib resistant and 27 % were imatinib intolerant . 2
AP = accelerated phase ; BP = blast phase ; CP = chronic phase .
hepatic enzyme tests monthly for the first 3 months and as clinically indicated . In patients with transaminase elevations , monitor liver enzymes more frequently . Drug-induced liver injury has occurred . Withhold , dose reduce , or discontinue BOSULIF as necessary . In patients with mild , moderate , or severe hepatic impairment , the recommended starting dose is 200 mg daily .
Renal Toxicity : An on-treatment decline in estimated glomerular filtration rate has occurred in patients treated with BOSULIF . Monitor renal function at baseline and during therapy , with particular attention to patients with preexisting renal impairment or risk factors . Consider dose adjustment in patients with baseline and treatment emergent renal impairment . The recommended starting doses for patients with severe renal impairment ( CrCL < 30 mL / min ) or moderate renal impairment ( CrCL 30-50 mL / min ) are 300 mg and 400 mg daily , respectively .
Fluid Retention : Fluid retention can occur and may cause pericardial effusion , pleural effusion , pulmonary edema , and / or peripheral edema . Monitor and manage patients using standards of care . Interrupt , dose reduce , or discontinue BOSULIF as necessary .