On Location
American Society of Hematology ’ s
58th ANNUAL MEETING & EXPOSITION
he 58th ASH Annual Meeting & Exposition featured practice-changing research from across the spectrum of hematologic malignancies and blood disorders . In this issue , ASH Clinical News is taking a look at the plenary and late-breaking abstracts presented at the meeting , including CAR T-cell therapy in non-Hodgkin lymphoma , a new selectin inhibitor for patients with sickle cell disease , and gene therapy for patients with hemophilia B .
Visit ashclinicalnews . org / on-location for our complete coverage of the meeting . ASH Clinical News was also on site to speak with presenters and moderators about the groundbreaking research that was shared at the meeting . Check out all of the interviews at ashclinicalnews . org / multimedia / exclusive-videos . And , new this year , look for more coverage in our special issue in mid-January , where we ’ ll take a deep dive into the 58th ASH Annual Meeting .
StaMINA : Second AHCT and Post-Transplant Consolidation Therapy Offer No Benefit Over Single Transplant
For patients with multiple myeloma ( MM ), more treatment does not necessarily mean better outcomes , according to results from the phase III StaMINA trial , which enrolled 758 transplant-eligible patients with symptomatic MM ( median age = 57 years ; range = 20-70 years ) in one of three treatment arms :
• Standard of care : melphalan 200 mg / m 2 plus autologous hematopoietic cell transplantation ( AHCT ; n = 257 )
• Consolidation : standard of care plus 4 cycles of consolidation ( lenalidomide 15 mg on days 1-14 ; dexamethasone 40 mg on days 1 , 8 , and 15 ; and bortezomib 1.3 mg / m 2 on days 1 , 4 , 8 , and 11 every 21 days ; n = 254 )
• Tandem : standard of care plus a second autologous hematopoietic cell transplanation ( AHCT ; n = 247 )
All patients had received at least two cycles of any regimen as initial systemic therapy and were within two to 12 months of the first dose of initial therapy at the time of enrollment . Patients were excluded if they had received prior HCT , were previously treated with melphalan > 50 mg intravenously , had disease progression prior to enrollment , or received lenalidomide as initial therapy for MM and have experienced toxicities resulting in treatment discontinuation .
All arms included maintenance therapy with lenalidomide 5 mg to 15 mg daily until progression .
At a median follow-up of 38 months , progression-free survival ( PFS ; defined as disease progression , initiation of non-protocol antimyeloma therapy , or death ) was not significantly improved in patients in the consolidation or tandem arms compared with the standard of care , at 52 percent in the standard-of-care arm , 57 percent in the consolidation arm , and 56 percent in the tandemtransplant arm ( p = 0.37 ). Rates of overall survival ( OS ) at 30 months were also similar among the three groups : 82.0 percent , 85.7 percent , and 83.4 percent , respectively . Median OS had not been reached at the time of presentation .
Thirty-nine patients ( 5.1 %) developed secondary malignancies , and these rates were similar across the three treatment arms ( 15 in the consolidation arm , 14 in the tandem-transplant arm , and 10 in the standard-of-care arm ). There was no difference in treatmentrelated mortality .
The investigators , led by Edward A . Stadtmauer , MD , section chief of hematologic malignancies at the Abramson Cancer Center at the University of Pennsylvania in Philadelphia , noted that the findings are limited by poor protocol adherence in the double AHCT arm ( 32 % of patients did not receive the planned second AHCT ). Future clinical trials are needed to examine the reasons for not proceeding to assigned treatment , as well as the correlation between MM biologic factors and outcomes .
The researchers concluded that AHCT plus lenalidomide maintenance therapy should remain the standard of care in MM . “ When compared with the current standard course of treatment alone , these data suggest that additions to standard MM therapy do not improve benefit for patients ,” Dr . Stadtmauer said during his presentation of the study results , adding that there is always room for improvement . “ New therapies and interventions need to be actively investigated to see how much they further benefit the early treatment of patients with myeloma . I believe it would be reasonable to compare any new treatments to the standard therapy of melphalan followed by a single AHCT followed by lenalidomide maintenance .”
REFERENCE
Stadtmauer EA , Pasquini MC , Blackwell B , et al . Comparison of autologous hematopoietic cell transplant ( autoHCT ), bortezomib , lenalidomide ( len ) and dexamethasone ( RVD ) consolidation with len maintenance ( ACM ), tandem autohct with len Maintenance ( TAM ) and autohct with len maintenance ( AM ) for up-front treatment of patients with multiple myeloma ( MM ): primary results from the randomized phase III trial of the Blood and Marrow Transplant Clinical Trials Network ( BMT CTN 0702 – StaMINA Trial ). Abstract LBA-1 . Presented at the 2016 ASH Annual Meeting , December 6 , 2016 ; San Diego , California .
Ibrutinib for the Treatment of Steroid- Refractory Chronic Graft-Versus-Host Disease After Transplant
The Bruton tyrosine kinase inhibitor ibrutinib is approved by the U . S . Food and Drug Administration ( FDA ) for the treatment of several B-cell malignancies and , according to results from a phase II study presented by David Miklos , MD , PhD , associate professor of medicine at the Stanford University Medical Center , it may also be a potential treatment option for hematopoietic cell transplantation patients with chronic graft-versus-host disease GVHD ( cGVHD ) whose disease has not responded to corticosteroids .
Early data from this trial served as the basis for the FDA ’ s decision in June 2016 to grant ibrutinib breakthrough therapy and orphan designation for the treatment of cGVHD after the failure of one or more lines of systemic therapy . Forty-two patients ( median age = 56 years ; range = 19-74 years ) with cGVHD who had been treated with a median of two prior regimens ( range = 1-3 ) received ibrutinib 420 mg . Median duration of cGVHD before study entry was 13.7 months ( range = 1.1-63.2 months ).
At a median follow-up of 13.9 months , two-thirds of patients ( n = 28 ) responded to ibrutinib treatment ( defined according to the 2005 National Institutes of Health consensus response criteria ), including nine who achieved a complete response ( CRs ; 21 %) and 19 who achieved a partial response ( PRs ; 45 %). Seventyone percent ( n = 20 / 28 ) and 48 percent ( n = 12 / 25 ) sustained responses of ≥20 and ≥32 weeks , respectively .
Five patients discontinued treatment due to progressive cGVHD , and another 14 patients discontinued due to adverse events ( AEs ). The most common AEs were fatigue ( 57 %), diarrhea ( 36 %), muscle spasms ( 29 %), nausea ( 26 %), and bruising ( 24 %). Grade ≥3 AEs occurring in three or more patients included pneumonia ( n = 6 ), fatigue ( n = 5 ), and diarrhea ( n = 4 ). Serious AEs occurred in 22 patients ( 52 %); grade ≥3 serious AEs were reported in 17 patients ( 40 %), including pneumonia ( n = 5 ), septic shock ( n = 2 ), and pyrexia ( n = 2 ). Two fatal events ( multilobular pneumonia and bronchopulmonary aspergillosis ) were reported .
“ Managing the ibrutinib-associated side effects will be important as we learn how to advise our patients going forward using this drug ,” Dr . Miklos said , noting that the AE rates with ibrutinib did not differ from the AE rates seen with corticosteroids alone . “ Also , 13 patients have been on ibrutinib for more than two years . They are coming off the therapy [ without cGVHD recurrence ], which is exciting because it means people are stopping all immune-suppressive therapies , which , of course , is the goal .”
In an accompanying exploratory biomarker study ,
26 ASH Clinical News January 2017