American Society of Hematology ’ s
On Location
American Society of Hematology ’ s
2017 ANNUAL MEETING & EXPOSITION
his month , we continue our coverage of the 59th ASH Annual Meeting & Exposition in Atlanta , Georgia , which featured practice-changing research from across the spectrum of hematologic malignancies and blood disorders .
In this special issue , ASH Clinical News is taking a look at the some of the new drugs , new indications , and new insights presented at the 2017 ASH Annual Meeting , including the first anti-sickling agent for sickle cell disease and research questioning the role of bleomycin in frontline Hodgkin lymphoma treatment .
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 .
Attendees browse the exhibit hall .
Newly Approved Drugs in ALL and NHL : How to Use Them in Practice
In 2017 , the U . S . Food and Drug Administration ( FDA ) approved several therapies for the treatment of hematologic malignancies , marking the first chimeric antigen receptor ( CAR ) T-cell therapies for any indication and the first antibody-drug conjugate for acute lymphocytic leukemia ( ALL ). As the number of treatment options for ALL and non-Hodgkin lymphoma ( NHL ) expands , so do questions about how these new agents should be incorporated into clinical practice .
At the 2017 ASH Annual Meeting , experts discussed the clinical applications of five newly approved treatments in the ASH-FDA Joint Symposium on New Drug Approvals in Acute Lymphocytic Leukemia and Non-Hodgkin Lymphoma :
• tisagenlecleucel – approved August 30 , 2017 , for the treatment of pediatric and young adult patients with B-cell precursor ALL that is refractory or in second or later relapse
• inotuzumab ozogamicin – approved August 17 , 2017 , for the treatment of adults with relapsed or refractory B-cell precursor ALL
• axicabtagene ciloleucel – approved October 18 , 2017 , for the treatment of patients with large B-cell lymphoma
• copanlisib – approved September 14 , 2017 , for the treatment of adult patients with relapsed follicular lymphoma ( FL )
• acalabrutinib – approved October 31 , 2017 , for the treatment of relapsed or refractory mantle cell lymphoma ( MCL )
The session , chaired by 2017 ASH President Kenneth C . Anderson , MD , was adapted from ASH ’ s webinar series on newly approved drugs . The webinars feature FDA reviewers discussing the approval decisions and clinicians with significant experience with the agents commenting on treatment challenges , including identification of the appropriate population , dosing , adverse events ( AEs ), and off-label use . “ There has been incredible progress over the last few years in all of the hematologic malignancies ,” Dr . Anderson said , citing the seven FDA approvals for myeloma treatments in the last two years . “ In the last year , we ’ ve had paradigm changes in ALL and NHL , as well .”
ALL
Tisagenlecleucel The FDA ’ s approval of the CAR T-cell therapy tisagenlecleucel to treat young patients ( ≤25 years old ) with B-cell precursor ALL that is refractory or is in second or later relapse made history as the first gene therapy available in the United States . The decision was based on complete remission ( CR ) rates in the U . S . population , explained Emily Jen , MD , PhD , clinical reviewer with the FDA . “ Within three months of tisagenlecleucel infusion , 63 percent achieved CR , and all patients with a CR or CR with incomplete count recovery also achieved minimal residual disease ( MRD ) negativity ,” she added . “ From an efficacy standpoint , tisagenlecleucel showed a substantial improvement over available therapy .”
Fatal adverse events ( AEs ) included infection ( 4 %) and intracerebral hemorrhage ( 1 %), and other common AEs ( reported in > 30 % of patients ) included cytokine release syndrome
( CRS ), hypogammaglobulinemia , infections , pyrexia , headache , encephalopathy , hypotension , and bleeding . The therapy carries boxed warnings for CRS and neurologic toxicities , and the treatment is only available under a Risk Evaluation and Mitigation Strategy ( REMS ).
As the first gene therapy approved in the U . S ., the approval of tisagenlecleucel represented “ a watershed moment in cancer immunotherapy ,” said Crystal L . Mackall , MD , professor of Pediatrics and Medicine at Stanford University in California , who discussed approvals in ALL . “ To me , the exciting point is that , in all the studies of anti-CD19 CAR T cell therapy in ALL , the highest-risk patients continually saw high rates of remission ,” she added . “ Despite the complexities in production and cost and [ toxicity ] issues , these therapies are still poised for a major impact in B-cell ALL .”
Dr . Mackall expressed concerns about CRS and neurotoxicities associated with these therapies , which may be unfamiliar to many hospitals . She noted that the observed toxicities are “ not a deal breaker .” The interleukin-6 receptor tocilizumab , which was approved simultaneously with tisagenlecleucel to manage CRS , has improved outcomes for patients who develop this AE . Researchers also are developing treatment algorithms , grading scales , and early predictors that can identify patients who would benefit from prophylactic treatment .
Early clinical trials with tisagenlecleucel were marred by challenges in manufacturing ; in the pivotal ELIANA trial , only 76 percent of children enrolled in the trial received the manufactured cells . “ It simply took too long to get these cells to the children ,” Dr . Mackall said . “ Accounting for these manufacturing failures , the response rate drops to 67 percent .”
26 ASH Clinical News January 2018 Annual Meeting Edition