On Location Conference Coverage
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CD19-directed therapy : Of the 82 patients who were evaluable for CD19 expression ( measured via immunochemistry ) at the time of follow-up , 90 percent were CD19 positive ; rates of ORR and CR were similar between CD19-positive and CD19- negative patients ( 85 % and 57 % vs . 75 % and 50 %, respectively ).
The most common grade ≥3 treatmentrelated AEs included neutropenia ( 66 %), leukopenia ( 44 %), anemia ( 43 %), febrile neutropenia ( 31 %), thrombocytopenia , ( 24 %), and encephalopathy ( 21 %).
Cytokine release syndrome ( CRS ) and neurologic toxicities were the AEs of most concern , given reports from
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other trials of CAR T-cell therapies . ( Earlier this year , Kite Pharmaceuticals , the manufacturer of KTE-C19 , reported that one patient enrolled in the safety expansion phase of ZUMA-1 died from cerebral edema , marking the first death from cerebral edema recorded in the KTE-C19 clinical trials program .) Thirteen percent and 28 percent of patients experienced severe , grade ≥3 CRS and neurologic events , respectively , but all of the events were resolved except for one grade 1 memory impairment .
In the subset of 70 patients who experienced CRS or neurologic events , 43 required treatment with tocilizumab and
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27 required treatment with tocilizumab and steroids , but these treatments did not decrease the efficacy of axicabtagene ciloleucel ( ORR = 84 % and 78 %, respectively ). “ These therapies kind of ‘ turn off ’ immune responses , but we found that patients who needed them had very similar response rates [ to those who did not ],” Dr . Locke said .
Three patients died during study follow-up , but , he added , “ considering that these patients are without any other treatment options , we think that the riskreward benefit is favorable .”
The study ’ s findings are limited by the short duration of follow-up and
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the single-arm design . Based on results from this trial , the manufacturers of axicabtagene ciloleucel submitted a biologics license application to the U . S . Food and Drug Administration for the treatment of patients with aggressive NHL who are ineligible for AHCT .
Dr . Locke reports research funding from Kite Pharma .
REFERENCE
Locke FL , Neelapu SS , Bartlett NL , et al . Clinical and biologic covariates of outcomes in ZUMA-1 : a pivotal trial of axicabtagene ciloleucel ( axi-cel ; KTE-C19 ) in patients with refractory aggressive non-Hodgkin lymphoma ( r-NHL ). Abstract # 7512 . Presented at the 2017 ASCO Annual Meeting , June 5 , 2017 ; Chicago , Illinois .
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Conference Coverage
BREAKTHROUGHS IN BLOOD DISORDERS
he European Hematology Association ’ s 22nd Congress was held June 22-25 in Madrid , Spain , where more than 10,000 international hematologists met to share the latest results from clinical and translational research in hematologic disorders and emerging techniques for diagnosis and risk assessment .
Here , ASH Clinical News presents highlights from the meeting , including a first-in-class pleiotropic pathway modifier for non-Hodgkin lymphomas , a risk-adapted treatment approach for young patients with acute myeloid leukemia , and the combination of danazol plus ATRA in immune thrombocytopenia .
CC-122 Plus Obinutuzumab Effective in Relapsed / Refractory B-Cell NHL
Combining the anti-CD20 monoclonal antibody obinutuzumab with the first-in-class pleiotropic pathway modifier CC-122 led to high response rates and durable remissions in patients with relapsed / refractory B-cell non-Hodgkin lymphoma ( NHL ), according to results from a phase Ib study presented at the 22nd Congress of the European Hematology Association .
CC-122 has immunomodulatory effects on T-cell and natural killer-cell function , which could result in “ potent anti-lymphoma effects ,” study co-author and presenter Réda Bouabdallah , MD , of the Institut Paoli-Calmettes in Marseille , France , explained .
In this multicenter , open-label , dose-escalation and doseexpansion study , researchers enrolled 38 patients ( median age = 60 years ; range = 26-81 years ) with three subtypes of B-cell NHL : diffuse large B-cell lymphoma ( DLBCL ) and follicular lymphoma ( FL ) or marginal zone lymphoma ( MZL ; n = 19 ).
TABLE 2 . Efficacy by NHL Type
All patients ( N = 38 )
DLBCL ( n = 19 )
FL / MZL ( n = 19 )
Overall response |
25 ( 66 %) |
9 ( 47 %) |
16 ( 84 %) |
Complete response |
12 ( 32 %) |
3 ( 16 %) |
9 ( 47 %) |
Partial response |
13 ( 34 %) |
6 ( 32 %) |
7 ( 37 %) |
Stable disease |
4 ( 11 %) |
3 ( 16 %) |
1 ( 5 %) |
Progressive disease |
6 ( 16 %) |
4 ( 21 %) |
2 ( 11 %) |
Not evaluable |
3 ( 8 %) |
3 ( 16 %) |
0 |
DLBCL = diffuse large B-cell lymphoma ; FL = follicular lymphoma ; MZL = |
marginal zone lymphoma |
Patients were eligible for inclusion if they had received one or more prior regimens for CD20-positive NHL , FL , or MZL , or two or more prior regimens and / or autologous hematopoietic cell transplantation ( AHCT ) for DLBCL . Patients received oral CC-122 in escalating doses ( administered on days 1-5 ), in combination with intravenous obinutuzumab 1,000 mg ( administered on days 2 , 8 , and 15 of cycle 1 and on day 1 of cycles 2-8 ), until disease progression or unacceptable toxicity .
At baseline , 21 percent of patients had bone marrow involvement with lymphoma . The median number of prior therapies was four ( range = 1-12 therapies ), and 14 patients ( 37 %) had undergone AHCT .
Patients received CC-122 for a median of 22 weeks ( range = 3-71 weeks ), which is equivalent to 6 cycles ( range = 1-18 cycles ). The overall response rate ( ORR ) was 66 percent , including a complete response rate of 32 percent ( n = 12 ) and a partial response rate of 34 percent ( n = 13 ; TABLE 2 ). Patients with FL or MZL appeared to have the highest ORR at 84 percent , compared with an ORR of 47 percent for patients with DLBCL ( p value not provided ).
The median time to best response was 57 days ( range = 56-114 days ), and the median duration of response was not yet reached .
In the dose-escalation trial , two patients ( 5 %) discontinued treatment because of adverse events ( AEs ) and two patients ( 5 %) experienced a dose-limiting toxicity . Ten patients ( 29 %) required a dose reduction of CC-122 , and 26 patients ( 76 %) required a temporary interruption of treatment – primarily related to AEs . For most patients ( 56 %), the treatment interruption was shorter than 1 week .
Sixty-five percent of patients experienced AEs . The most common ( ≥10 %) grade 3 / 4 AEs were neutropenia ( 50 %) and thrombocytopenia ( 21 %). Fifteen patients ( 44 %) had one or more serious AEs , including two cases of febrile neutropenia ( related to CC-122 ), two cases of cytokine release syndrome ( related to obinutuzumab ), and two cases of pneumonia . Three patients died during the study ( 2 from progressive disease ; 1 related to AEs ).
The results of this early study are limited by the small sample size and the lack of a comparator arm . Dr . Bouabdallah noted that , at the time of presentation , “ the 30 patients receiving CC-122 at a dose of 3 mg and higher have shown the best and most durable response ,” and 3 mg is being used as the recommended dose for a phase II trial of CC-122 plus obinutuzumab .
The authors report no relevant conflicts of interest .
REFERENCE
Michot JM , Bouabdallah R , Doorduijn JK , et al . CC-122 in combination obinutuzumab : a phase 1b study to relapsed or refractory patients with diffuse large B-cell lymphoma , follicular lymphoma , or marginal zone lymphoma . Abstract # S467 . Presented at the 22nd Congress of the European Hematology Association , June 24 , 2017 ; Madrid , Spain .
Danazol Plus ATRA Safe and Effective in Corticosteroid- Resistant / Relapsed ITP
According to results from a multicenter , prospective study presented at the 22nd Congress of the European Hematology Association , the combination of all-trans retinoid acid ( ATRA ) and danazol may improve sustained response in
34 ASH Clinical News July 2017 Bonus Mid-Year Edition