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ASH Consultative Hematology Course
September 7 , 2017 Chicago , IL ( prior to the 2017 ASH Meeting on Hematologic Malignancies )
December 11 , 2017 Atlanta , GA ( during the 2017 ASH Annual Meeting ) An interactive , half-day program in which participants engage in case-based presentations and discussions focusing on non-malignant hematology topics such as thrombosis , thrombocytopenia , and bleeding .
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Atlanta , GA |
7th International Symposium on Acute Promyelocytic Leukemia
September 24 – 27 , 2017 Rome , Italy In addition to advances in biology and treatment of acute promyelocytic leukemia , the meeting includes updates on diagnostics , management , and minimal residual disease assessment .
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American Society for Radiation Oncology Annual Meeting
September 24 – 27 , 2017 San Diego , CA The 58th ASTRO Annual Meeting creates a forum for global collaboration on issues in radiation oncology .
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Table 4 Summary of Adverse Reactions Reported in ≥ 5 % of Patients with CLL and at Least 2 % Greater in the GAZYVA Treated Arm ( Stage 2 )
Adverse Reactions System Organ Class
Table 5 Post-Baseline Laboratory Abnormalities by CTCAE Grade in ≥ 5 % of Patients with CLL and at Least 2 % Greater in the GAZYVA Treated Arm ( Stage 2 )
Laboratory Abnormalities
GAZYVA + Chlorambucil n = 336
All Grades %
GAZYVA + Chlorambucil n = 336
All Grades %
Grades 3 – 4 %
Grades 3 – 4 %
Rituximab + Chlorambucil n = 321
a
Adverse reactions reported under “ Blood and lymphatic system disorders ” reflect those reported by investigator as clinically significant .
Rituximab + Chlorambucil n = 321
All Grades Grades % 3 – 4 %
Summary of Clinical Trial Experience in Non-Hodgkin Lymphoma The safety of GAZYVA was evaluated based on a safety population of 392 patients with indolent NHL , of whom 81 % had FL . In the population of patients with FL , the profile of adverse reactions was consistent with the overall indolent NHL population . Patients were treated with either GAZYVA in combination with bendamustine , followed by GAZYVA monotherapy in patients that have not progressed , or with bendamustine alone .
Patients randomized to the GAZYVA + bendamustine arm received three weekly 1000 mg doses of GAZYVA in the first cycle and a single dose of 1000 mg once every 28 days for 5 additional cycles in combination with bendamustine 90 mg / m 2 on Days 1 and 2 in all 6 cycles . Patient randomized to the bendamustine alone arm received 120 mg / m 2 on Days 1 and 2 . This regimen continued for 6 cycles of 28 days in duration . For patients who did not progress on GAZYVA in combination with bendamustine , a single dose of 1000 mg GAZYVA monotherapy was given every two months until progression or for a maximum of two years . During combination therapy with GAZYVA and bendamustine , 79 % of patients received all 6 treatment cycles of GAZYVA and 76 % received all 6 treatment cycles of bendamustine compared to 67 % of patients in the bendamustine alone arm .
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The most common adverse reactions ( incidence ≥ 10 %) observed in patients with iNHL in the GAZYVA containing arm were infusion reactions , neutropenia , nausea , fatigue , cough , diarrhea , constipation , pyrexia , thrombocytopenia , vomiting , upper respiratory tract infection , decreased appetite , arthralgia , sinusitis , anemia , asthenia and urinary tract infection .
The most common Grade 3-4 adverse reactions ( incidence ≥ 10 %) observed in patients with iNHL in the GAZYVA containing arm were neutropenia , thrombocytopenia and infusion reactions .
Table 6 Summary of Adverse Reactions Reported in ≥5 % of Patients with Indolent NHL and at Least 2 % Greater in the GAZYVA plus Bendamustine Followed by GAZYVA Monotherapy Treated Arm
Adverse Reactions System Organ Class
GAZYVA + Bendamustine followed by GAZYVA monotherapy n = 194
All Grades %
Grades 3-4 %
Bendamustine n = 198
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a Defined as any related adverse reaction that occurred during or within 24 hours of infusion .
During the monotherapy period with GAZYVA , the most common adverse reactions in patients with iNHL were cough ( 15 %), upper respiratory tract infections ( 12 %), neutropenia ( 11 %), sinusitis ( 10 %), diarrhea ( 8 %), infusion related reactions ( 8 %), nausea ( 8 %), fatigue ( 8 %), bronchitis ( 7 %), arthralgia ( 7 %), pyrexia ( 6 %), nasopharyngitis ( 6 %), and urinary tract infections ( 6 %). The most common Grade 3-4 adverse reactions during the monotherapy period were neutropenia ( 10 %), and anemia , febrile neutropenia , thrombocytopenia , sepsis , upper respiratory tract infection , and urinary tract infection ( all at 1 %).
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Table 7 Post-Baseline Laboratory Abnormalities by CTCAE Grade in ≥ 5 % of Patients with iNHL and at Least 2 % Greater in the GAZYVA plus Bendamustine Followed by GAZYVA Monotherapy Treated Arm a
Laboratory Abnormalities
GAZYVA + Bendamustine followed by GAZYVA monotherapy n = 194
All Grades %
Grades 3 – 4 %
a Two percent different in either the All Grades or Grade 3-4 Lab Abnormalities . In the monotherapy phase of treatment with GAZYVA , the most frequently reported hematological laboratory abnormalities were lymphopenia ( 80 %), leukopenia ( 63 %), low hemoglobin ( 50 %) and neutropenia ( 46 %). The most frequently reported hematological Grade 3-4 laboratory abnormalities during the monotherapy period were lymphopenia ( 52 %), neutropenia ( 27 %) and leukopenia ( 20 %).
In the monotherapy phase of treatment with GAZYVA , the most frequently reported chemistry laboratory abnormalities were elevated creatinine ( 69 %), decreased creatinine clearance ( 43 %), hypophosphatemia ( 25 %), AST / SGOT increased ( 24 %) and ALT / SGPT increased ( 21 %). The most frequently reported chemistry Grade 3-4 laboratory abnormalities during the monotherapy period were hypophosphatemia ( 5 %) and hyponatremia ( 3 %).
Infusion Reactions : Chronic Lymphocytic Leukemia The incidence of infusion reactions was 65 % with the first infusion of GAZYVA . The incidence of Grade 3 or 4 infusion reactions was 20 % with 7 % of patients discontinuing therapy . The incidence of reactions with subsequent infusions was 3 % with the second 1000 mg and < 1 % thereafter . No Grade 3 or 4 infusion reactions were reported beyond the first 1000 mg infused .
Of the first 53 patients receiving GAZYVA on the trial , 47 ( 89 %) experienced an infusion reaction . After this experience , study protocol modifications were made to require premedication with a corticosteroid , antihistamine , and acetaminophen . The first dose was also divided into two infusions ( 100 mg on day 1 and 900 mg on day 2 ). For the 140 patients for whom these mitigation measures were implemented , 74 patients ( 53 %) experienced a reaction with the first 1000 mg ( 64 patients on day 1 , 3 patients on day 2 , and 7 patients on both days ) and < 3 % thereafter [ see Dosage and Administration ( 2 )].
Non-Hodgkin Lymphoma Overall , 69 % of patients experienced an infusion reaction ( all grades ) during treatment with GAZYVA in combination with bendamustine . The incidence of Grade 3-4 infusion reactions was 11 %. In Cycle 1 , the incidence of infusion reactions ( all grades ) was 55 % in patients receiving GAZYVA in combination with bendamustine with Grade 3-4 infusion reactions reported in 9 %. In patients receiving GAZYVA in combination with bendamustine , the incidence of infusion reactions was highest on Day 1 ( 38 %), and gradually decreased on Days 2 , 8 and 15 ( 25 %, 7 % and 4 %, respectively ).
During Cycle 2 , the incidence of infusion reactions was 24 % in patients receiving GAZYVA in combination with bendamustine and decreased with subsequent cycles .
During GAZYVA monotherapy , infusion reactions ( all grades ) were observed in 8 % of patients . No grade 3-4 infusion reactions were reported during GAZYVA monotherapy .
Overall , 2 % of patients experienced an infusion reaction leading to discontinuation of GAZYVA .
Neutropenia : Chronic Lymphocytic Leukemia The incidence of neutropenia reported as an
Bendamustine n = 198
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