CLINICAL NEWS the researchers found that pro-inflammatory , chemotactic , and fibrotic factors ( including the GVHD-associated biomarkers IFNγ , TNFα , IP-10 , and CXCL9 ) decreased while patients were receiving ibrutinib . These results were “ consistent with decreasing inflammation and improving patients ’ immune reconstitution ,” Dr . Miklos said .
The study had no comparator arm , which limits its findings , the researchers noted . Dr . Miklos added that a
PERSIST-2 : Pacritinib Compared With Best Available Therapy for Patients With Myelofibrosis and Thrombocytopenia
In the phase III PERSIST-2 trial , the multi-tyrosine kinase inhibitor pacritinib met one of two co-primary endpoints , demonstrating a significant reduction in spleen volume compared with best available treatment in patients with myelofibrosis ( MF ) and thrombocytopenia . The co-primary endpoint of reduction of Total Symptom Score ( TSS ) was not significantly improved with pacritinib , though .
“ The JAK 1 / 2 inhibitor ruxolitinib is the only approved therapy for patients with intermediate or higher-risk MF and a platelet count > 50,000 /µ L ,” lead author John Mascarenhas , MD , from the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai in New York randomized , controlled trial comparing upfront treatment with ibrutinib or high-dose steroids in patients with cGVHD and other trials are questioning whether ibrutinib could prevent cGVHD when used as maintenance therapy post-transplant .
REFERENCE
Miklos D , Cutler CS , Arora M , et al . Multicenter open-label phase 2 study of ibrutinib in chronic graft versus host disease ( cGVHD ) after failure of corticosteroids . Abstract LBA-3 . Presented at the 2016 ASH Annual Meeting , December 6 , 2016 ; San Diego , California .
City , told ASH Clinical News . “ Earlier in its development , pacritinib showed efficacy in reducing spleen volume and symptom burden , as well as less myelosuppression than ruxolitinib , which opens up a niche , particularly in patients with low platelet counts .”
A total of 311 patients with MF and platelet counts ≤100,000 /µ L were randomized to receive either pacritinib 200 mg twice daily , pacritinib 400 mg once daily , or BAT ( including ruxolitinib ). At the time of the presentation , data were evaluable for 221 patients : 74 in the pacritinib twice daily dosing group , 75 in the pacritinib once daily dosing group , and 72 in the BAT group . Nearly half of patients in the BAT group ( 44 %) received ruxolitinib at some point during the study .
From baseline to week 24 , a higher percentage of patients in the pooled pacritinib arms achieved spleen volume reduction ( SVR ) ≥35 percent ( a coprimary endpoint ) than in the BAT arm : 18 percent ( n = 27 / 149 ) versus 3 percent ( n = 2 / 72 ; p = 0.001 ). The second co-primary endpoint ( the proportion of patients achieving > 50 % reduction in TSS from baseline to week 24 ) was not met : 25 percent of pacritinib-treated patients ( n = 37 / 149 ) had a reduction in symptom burden , compared with 14 percent of BAT patients ( n = 10 / 72 ; p = 0.079 ).
However , Dr . Mascarenhas noted that in secondary analyses looking at each pacritinib dosing cohort , twice-daily dosing demonstrated a significant improvement over BAT for both endpoints : 22 percent versus 3 percent achieved SVR ≥35 % ( p = 0.001 ), and 32 percent versus 14 percent achieved ≥50 % reduction in TSS ( p = 0.011 ).
“ Unfortunately , the TSS co-primary endpoint was not met , but the data show that pacritinib has activity , particularly at twice-daily dosing ,” he said .
However , safety is still a concern , as the FDA placed pacritinib on full clinical hold in February 2016 due to concerns over excess deaths and cardiac and hematologic toxicities . In PERSIST-2 , hazard ratios for OS , compared with BAT , were 0.68 for twice-daily pacritinib and 1.18 for once-daily pacritinib .
During PERSIST-2 , 10 ( 9 %), 15 ( 14 %), and 15 ( 14 %) patients died on twice-daily pacritinib , once-daily pacritinib , and BAT , respectively . The most common treatment-emergent AEs associated with pacritinib were gastrointestinal ( diarrhea , nausea , and vomiting ) and hematologic ( anemia and thrombocytopenia ).
Before future trials can determine the safety of pacritinib and its optimal dosing , the drug ’ s manufacturer will need to negotiate with the FDA to lift the clinical hold on pacritinib .
REFERENCE
Mascarenhas J , Hoffman R , Talpaz M , et al . Results of the Persist-2 phase 3 study of pacritinib ( PAC ) versus best available therapy ( BAT ), including ruxolitinib ( RUX ), in patients ( pts ) with myelofibrosis ( MF ) and platelet counts < 100,000 /µ l . Abstract LBA-5 . Presented at the 2016 ASH Annual Meeting , December 6 , 2016 ; San Diego , California .
Anti-CD19 CAR T-Cell Therapy Has High Response Rate in Refractory , Aggressive Non-Hodgkin Lymphoma
For patients with chemo-refractory , aggressive non-Hodgkin lymphoma ( NHL ), treatment with anti-CD19 chimeric antigen receptor ( CAR ) T-cell therapy ( known as KTE- C19 ) induced a CR rate that was nearly six times higher than what has typically been seen historically , according to results from the phase II ZUMA-1 trial , the first multicenter trial of this immunotherapy-based approach in patients with aggressive NHL .
The study was conducted at 22 institutions and enrolled 111 patients into two cohorts : those with diffuse large B-cell lymphoma ( DLBCL ) and those with primary mediastinal B- cell lymphoma or transformed follicular lymphoma . Sattva S . Neelapu , MD , from the MD Anderson Cancer Center at the University of Texas in Houston , presented the results of an interim analysis of patients with DLBCL .
At the time of data presentation , 51 patients ( median age = 58 years ; range = 25-76 years ) were eligible for analysis ; 78 percent were refractory to two or more previous lines of therapy , 20 percent had relapsed within 12 months after AHCT , and 61 percent were treated with three or more lines of prior therapy .
The overall response rate ( ORR ; the study ’ s primary endpoint ) was 76 percent , which compared favorably with the historical control assumption of 20 percent ( p < 0.001 ), Dr . Neelapu reported . The rates of CRs and PRs were 47 percent and 29 percent , respectively .
Nearly all of these responses ( 92 %) occurred rapidly , within the first month of treatment , and 39 percent of patients had ongoing responses at three months .
“ Several patients have continued treatment for months , and [ some ] patients are experiencing complete remissions lasting one year or longer ,” Dr . Neelapu told ASH Clinical News . “ KTE-C19 was also tested previously in single-institution trials , which found that [ some ] patients who achieved a complete remission can have ongoing remissions nearly four years later .”
The most common grade ≥3 treatment-emergent AEs were neutropenia ( 67 %), anemia ( 39 %), thrombocytopenia ( 29 %), febrile neutropenia ( 27 %), and encephalopathy ( 24 %). The two most common side effects of KTE-C19 were cytokine release syndrome ( CRS ) and neurologic events , which occurred in 20 percent and 29 percent of patients , respectively . “ The majority of patients had grade 1 and grade 2 CRS ,” Dr . Neelapu said . “ We found only 13 percent of these patients developed grade ≥3 CRS .” He added that “ neurologic side effects were reversible in the majority of the patients .”
“ While this product appears to induce a high ORR , there is still room to improve the CR rates in these patients ,” he added . The researchers are conducting additional biomarker analyses to understand the main drivers for neurologic AEs and CRS , as well as why some patients relapse after achieving a CR or PR . Response duration is still being assessed .
REFERENCE
Neelapu SS , Locke FL , Bartlett N , et al . Kte-C19 ( anti-CD19 CAR T cells ) induces complete remissions in patients with refractory diffuse large B-cell lymphoma ( DLBCL ): results from the pivotal phase 2 ZUMA-1 . Abstract LBA-6 . Presented at the 2016 ASH Annual Meeting , December 6 , 2016 ; San Diego , California . Opening paragraph with bold and italic examples .
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