ASH Clinical News July 2017 V2 - Page 30

On Location

Conference Coverage

UPDATES IN MALIGNANT HEMATOLOGY

SH Clinical News was on site at this year ’ s American Society of Clinical Oncology ( ASCO ) Annual Meeting in Chicago to bring you the latest advances in malignant hematology presented at the meeting , including chimeric antigen receptor ( CAR ) T-cell therapy in myeloma and a novel JAK1 / 2 inhibitor for patients with myelofibrosis .
Visit ashclinicalnews . org / on-location and ashclinicalnews . org / multimedia for more of our news and exclusive videos . Also , look for more coverage of the practice-changing research shared at the meeting in our special issue in mid-July .

Early Results of CAR T-Cell Therapy in Myeloma Are “ Encouraging ”

In an ongoing , phase I trial of chimeric antigen receptor ( CAR ) T-cell therapy in patients with relapsed / refractory myeloma , 33 out of 35 patients achieved complete response ( CR ) or very good partial response ( VGPR ), for a clinical remission rate of 94 percent . Author Wanhong Zhao , MD , PhD , from the Second Affiliated Hospital of Xi ’ an Jiaotong University in Shaanxi , China , who presented the results as a late-breaking abstract , called the findings an “ encouraging breakthrough ” for myeloma patients .
“ Although recent advances in chemotherapy have prolonged life expectancy in multiple myeloma ( MM ), this cancer remains incurable ,” Dr . Zhao said during a press briefing . “ It appears that with this novel immunotherapy there may be a chance for cure in MM , but we will need to follow patients much longer to confirm that .” Dr . Zhao and researchers evaluated LCAR-B38M CAR T cells targeting B-cell maturation antigen ( BCMA ). The median number of infused cells was 4.7x10 6 / kg ( range = 0.6-7.0x10 6 / kg ).
The trial followed patients for a median of 208 days ( range = 62-321 days ), finding an objective response rate ( ORR ) of 100 percent . Thirty-three patients ( 94 %) achieved CR or VGPR within 2 months of CAR T-cell infusion .
At the time of data presentation , 19 patients had been followed for longer than 4 months , which the researchers selected as a pre-specified point for efficacy assessment ( per International Myeloma Working Group consensus guidelines ). In this subset of patients , 14 had achieved stringent CR , four had achieved VGPR , and one had achieved PR .
One patient in VGPR had evidence of disease progression , when an extramedullary lesion reappeared 3 months after a negative computed tomography scan , Dr . Zhao noted . However , there have been no relapses among patients in stringent CR . Five patients have been followed for more than a year ( 12-14 months ), and all remain in stringent CR and free of minimal residual disease .
“ LCAR-B38M technology not only demonstrates outstanding efficacy , but also suggests a great safety profile ,” Dr . Zhao said . The most common adverse event ( AE ) associated with CAR T-cell therapy , cytokine release syndrome ( CRS ), occurred in 85 percent of the patient population , but was transient in all patients . CRS was successfully managed with the interleukin-6 receptor tocilizumab .
Wanhong Zhao , MD , PhD
Other AEs were “ mild and manageable ,” the authors reported , and included fever , hypotension , and dyspnea . No patients experienced neurologic AEs , which have been serious complications in other trials of CAR T-cell therapies .
The study is limited by its small patient population and short follow-up . The researchers plan to eventually enroll a total of 100 patients , and , “ in early 2018 , we also plan to launch a similar clinical trial in the United States ,” Dr . Zhao said . “ Looking ahead , we would like to explore whether BCMA CAR T-cell therapy benefits patients who are newly diagnosed with MM .”
REFERENCE
Fan F , Zhao W , Liu J , et al . Durable remissions with BCMA specific chimeric antigen receptor ( CAR )-modified T cells in patients with refractory / relapsed multiple myeloma . Abstract # LBA3001 . Presented at the 2017 ASCO Annual Meeting , June 6 , 2017 ; Chicago , Illinois .

Daratumumab-Based Quadruplet Combination Is Safe in Newly Diagnosed Myeloma

In November 2016 , the U . S . Food and Drug Administration approved the anti-CD38 monoclonal antibody daratumumab in combination with two standard-of-care regimens ( dexamethasone plus lenalidomide or bortezomib ), after clinical trials showed that the addition of daratumumab prolonged progression-free survival ( PFS ) in patients with relapsed or refractory multiple myeloma ( MM ).
In an open-label , phase I study , investigators evaluated whether adding the proteasome inhibitor carfilzomib to the daratumumab , lenalidomide , and dexamethasone combination could further improve response rates , without increasing toxicity , in patients with newly diagnosed MM .
Andrzej J . Jakubowiak , MD , PhD , director of the myeloma program at The University of Chicago Medicine in Illinois , and co-authors evaluated the quadruplet combination in 22 patients ( median age = 60 years ; range = 24-74 years ) with newly diagnosed MM .
28 ASH Clinical News July 2017
On Location Conference Coverage UPDATES IN MALIGNANT HEMATOLOGY SH Clinical News was on site at this year’s American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago to bring you the latest advances in malignant hematology presented at the meeting, including chimeric antigen receptor (CAR) T-cell therapy in myeloma and a novel JAK1/2 inhibitor for patients with myelofibrosis. Visit ashclinicalnews.org/on-location and ashclinicalnews.org/ multimedia for more of our news and exclusive videos. Also, look for more coverage of the practice-changing research shared at the meeting in our special issue in mid-July. Early Results of CAR T-Cell Therapy in Myeloma Are “Encouraging” In an ongoing, phase I trial of chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed/refractory my- eloma, 33 out of 35 patients achieved com- plete response (CR) or very good partial response (VGPR), for a clinical remission rate of 94 percent. Author Wanhong Zhao, MD, PhD, from the Second Affiliated Hospital of Xi’an Jiaotong University in Shaanxi, China, who presented the results as a late-breaking abstract, called the find- ings an “encouraging breakthrough” for myeloma patients. “Although recent advances in chemo- therapy have prolonged life expectancy in multiple myeloma (MM), this cancer remains incurable,” Dr. Zhao said during a press briefing. “It appears that with this novel immunotherapy there may be a chance for cure in MM, but we will need to follow patients much longer to confirm that.” Dr. Zhao and researchers evaluated LCAR-B38M CAR T cells targeting B-cell maturation antigen (BCMA). The median number of infused cells was 4.7x10 6 /kg (range = 0.6-7.0x10 6 /kg). The trial followed patients for a median of 208 days (range = 62-321 days), find- ing an objective response rate (ORR) of 100 percent. Thirty-three patients (94%) achieved CR or VGPR within 2 months of CAR T-cell infusion. At the time of data presentation, 19 patients had been followed for longer than 4 months, which the researchers selected as a pre-specified point for efficacy as- sessment (per International Myeloma Working Group consensus guidelines). In this subset of patients, 14 had achieved stringent CR, four had achieved VGPR, Wanhong Zhao, MD, PhD and one had achieved PR. One patient in VGPR had evidence of disease progression, when an extramedul- lary lesion reappeared 3 months after a negative computed tomography scan, Dr. Zhao noted. However, there have been no relapses among patients in stringent CR. Five patients have been followed for more than a year (12-14 months), and all remain in stringent CR and free of minimal residual disease. “LCAR-B38M technology not only demonstrates outstanding efficacy, but also suggests a great safety profile,” Dr. Zhao said. The most common adverse event (AE) associated with CAR T-cell therapy, cytokine release syndrome (CRS), occurred in 85 percent of the patient population, but was transient in all patients. CRS was suc- cessfully managed with the interleukin-6 receptor tocilizumab. Other AEs were “mild and manageable,” the authors reported, and included fever, hypotension, and dyspnea. No patients experienced neurologic AEs, which have been serious complications in other trials of CAR T-cell therapies. The study is limited by its small patient population and short follow-up. The researchers plan to eventually enroll a total of 100 patients, and, “in early 2018, we also plan to launch a similar clinical trial in the United States,” Dr. Zhao said. “Looking ahead, we would like to explore whether BCMA CAR T-cell therapy benefits pa- tients who are newly diagnosed with MM.” REFERENCE Fan F, Zhao W, Liu J, et al. Durable remissions with BCMA specific chimeric antigen receptor (CAR)-modified T cells in patients with refractory/ relapsed multiple myeloma. Abstract #LBA3001. Presented at the 2017 ASCO Annual Meeting, June 6, 2017; Chicago, Illinois. Daratumumab-Based Quadruplet Combination Is Safe in Newly Diagnosed Myeloma In November 2016, the U.S. Food and Drug Administration approved the anti-CD38 monoclonal antibody daratumumab in combination with two standard-of-care regimens (dexamethasone plus lenalidomide or bortezomib), after clinical trials showed that the addition of daratumumab prolonged progression-free survival (PFS) in patients with relapsed or refractory multiple myeloma (MM). In an open-label, phase I study, investigators WfVFVBvWFW"FFrFR&FVЧ6R憖&F"6&fǦ֖"FFRF&GVV"VƖF֖FRBFWWF6P6&F6VBgW'FW"&fR&W76R&FW2vFWB7&V6rF6GFVG0vFWvǒFv6VBG'VV&vBBF&V7F"bFRזV&w&BFPVfW'6Gb66vVF6RƖ2B6WF'2WfVFVBFRVG'WW@6&F#"FVG2VFvRcV'3&vR#BsBV'2vFWvǐFv6VB#46Ɩ6Ww0Vǒ#