ASH Clinical News July 2017 V2 - Page 5

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 .
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 .
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 .
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
All
Grades
Grades %
3 – 4 %
Injury , poisoning and procedural complications
Infusion
66
20
38
4
reactions
Blood and lymphatic system disorders a
Neutropenia
38
33
32
28
Thrombocytopenia 14
10
7
3
Leukopenia
6
4
2
< 1
General disorders and administration site
conditions
Pyrexia
9
< 1
7
< 1
Gastrointestinal disorders
Diarrhea
10
2
8
< 1
Constipation
8
0
5
0
Infections and infestations
Nasopharyngitis
6
< 1
3
0
Urinary tract
5
1
2
< 1
infection
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 %
Hematology Neutropenia
76
46
69
41
Lymphopenia
80
39
50
16
Leukopenia
84
35
62
16
Thrombocytopenia 48
13
40
8
Anemia
39
10
37
10
Chemistry Hypocalcemia
37
3
32
< 1
Hypokalemia
14
1
10
< 1
Hyponatremia
26
7
18
2
AST / SGOT
27
2
21
< 1
increased ALT / SGPT
28
2
21
1
increased
Hypoalbuminemia 23
< 1
16
< 1
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 .
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
All
Grades
Grades %
3-4 %
Injury , Poisoning and Procedural Complications
Infusion related
69
11
63
6
reactions a
Blood and Lymphatic System Disorders
Neutropenia
35
33
28
26
Gastrointestinal Disorders
Constipation
19
0
16
0
Dyspepsia
5
0
3
0
General Disorders and Administration Site
Conditions
Pyrexia
18
1
14
0
Asthenia
11
1
8
0
Infections and Infestations
Upper Respiratory 13
2
8
1
Tract Infection
Sinusitis
12
1
5
0
Urinary Tract
10
3
6
0
Infection Nasopharyngitis
9
0
4
0
Musculoskeletal and Connective Tissue
Disorders
Arthralgia
12
0
5
0
Pain in Extremity
9
1
4
0
Respiratory , Thoracic and Mediastinal
Disorders
Cough
26
0
17
0
Nasal Congestion
7
0
2
0
Skin and Subcutaneous Tissue Disorders
Pruritus
9
0
6
0
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 %).
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 %
Hematology Neutropenia
75
52
77
42
Leukopenia
86
47
88
34
Lymphopenia
99
93
99
85
Chemistry Hypocalcemia
38
2
26
2
Hypophosphatemia 41
7
38
7
ALT / SGPT
35
1
31
4
increased
Elevated creatinine 87
4
92
2
Creatinine Clearance 58
6
61
4
( decreased )
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
All
Grades
Grades %
3 – 4 %
ASH Consultative Hematology Course 7th International Symposium on Acute Promyelocytic Leukemia September 7, 2017 Chicago, IL (prior to the 2017 ASH Meeting on Hematologic Malignancies) 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. 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. 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 GAZYVA + Chlorambucil n = 336 All Grades % Grades 3–4 % Rituximab + Chlorambucil n = 321 All Grades Grades % 3–4 % Injury, poisoning and procedural complications Infusion reactions 66 20 38 4 Blood and lymphatic system disorders a Neutropenia 38 Thrombocytopenia 14 Leukopenia 6 33 10 4 32 7 2 28 3 < 1 General disorders and administration site conditions Pyrexia 9 < 1 7 < 1 2 0 8 5 < 1 0 < 1 1 3 2 0 < 1 Gastrointestinal disorders Diarrhea Constipation 10 8 Infections and infestations Nasopharyngitis Urinary tract infection a 6 5 Adverse reactions reported under “Blood and lymphatic system disorders” reflect those reported by investigator as clinically significant. 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 Grades % 3–4 % Rituximab + Chlorambucil n = 321 All Grades Grades % 3–4 % Hematology Neutropenia Lymphopenia Leukopenia Thrombocytopenia Anemia 76 80 84 48 39 46 39 35 13 10 69 50 62 40 37 41 16 16 8 10 37 14 26 27 3 1 7 2 32 10 18 21 < 1 < 1 2 < 1 28 2 21 1 23 < 1 16 < 1 Chemistry Hypocalcemia Hypokalemia Hyponatremia AST/SGOT increased ALT/SGPT increased Hypoalbuminemia 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. Atlanta, GA 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 Bendamustine followed by n = 198 GAZYVA monothe &@w&FW0w&FW0w&FW2P2BRw&FW2R2BPW'6rB&6VGW&6Ɩ6F0gW6&VFV@&V7F2cc0`&BBǖF277FVF6&FW'0WWG&V3P30##`v7G&FW7FF6&FW'067FF`G7W6P0vVW&F6&FW'2BF֖7G&F6FP6FF0&W@7FVfV7F2BfW7FF0WW"&W7&F'0 G&7BfV7F6W6F0 PW&'G&7@0`fV7F6'vF0@W67V6VWFB6V7FfRF77VPF6&FW'0'F&v PWG&V֗G@&W7&F'F&62BVF7FF6&FW'06Vv#`p66vW7Fp 6B7V&7WFVW2F77VRF6&FW'0'W&GW0`FVfVB2&VFVBGfW'6R&V7FFB67W'&VBGW&r vF#BW'2bgW6GW&rFRFW&W&BvFtdFP7B6GfW'6R&V7F2FVG2vFvW&R6VvRRWW"&W7&F'G&7@fV7F2"RWWG&VR6W6F0RF'&VRgW6&VFVB&V7F0RW6VRfFwVRR'&6F2rR'F&vrR&WbR6'vF2bRBW&'G&7BfV7F2bRFR7B6w&FR2BGfW'6R&V7F2GW&rFRFW&W&BvW&RWWG&VRBV֖fV'&PWWG&VF&&7FV6W62WW &W7&F'G&7BfV7FBW&'G&7BfV7FࢆBRF&Rr7B&6VƖR&&F'&&ƗFW2'5D4Rw&FR(RRR`FVG2vFBBV7B"Rw&VFW FRtdW2&VFW7FRfvV@'tdFW&G&VFVB&&&F'&&ƗFW0td&VFW7FP&VFW7FPfvVB'tdFW&@w&FW0w&FW0w&FW2P>( 3BRw&FW2R>( 3BPVFwWWG&VWVVǖV6V֗7G'66V֖7FV֖B4u@7&V6V@VWfFVB7&VFP7&VFR6V&6PFV7&V6VBsP`S Cp2spC 3@P3C3R p#`33 p@pS@b c @GvW&6VBFffW&VBVFW"FRw&FW2"w&FR2B &&ƗFW2खFRFW&6RbG&VFVBvFtdFR7Bg&WVVFǒ&W'FVBVFv6&&F'&&ƗFW2vW&RǖVRWVVc2RrVv&SR@WWG&VCbRFR7Bg&WVVFǒ&W'FV@VFv6w&FR2B&&F'&&ƗFW0GW&rFRFW&W&BvW&RǖVS"RWWG&V#rRBWVV#RखFRFW&6RbG&VFVBvFtdFR7Bg&WVVFǒ&W'FVB6V֗7G'&&F'&&ƗFW2vW&RVWfFVB7&VFPcRFV7&V6VB7&VFR6V&6RC2R7FV֖#RR5B4tB7&V6V@#BRBB4uB7&V6VB#RFR7@g&WVVFǒ&W'FVB6V֗7G'w&FR2B&&F'&&ƗFW2GW&rFRFW&W&BvW&P7FV֖RRBG&V֖2RखgW6&V7F36&2ǖ7F2WVV֖FR6FV6RbgW6&V7F2v2cRRvFFRf'7BgW6btdFR6FV6R`w&FR2"BgW6&V7F2v2#RvFrPbFVG2F66FVrFW&FR6FV6R`&V7F2vF7V'6WVVBgW62v22RvFFP6V6BrBRFW&VgFW"w&FR0"BgW6&V7F2vW&R&W'FVB&WBFRf'7@rgW6VBbFRf'7BS2FVG2&V6VfrtdFPG&CrRWW&V6VBgW6&V7FgFW F2WW&V6R7GVG&F6Ff6F2vW&PFRF&WV&R&VVF6FvF6'F67FW&BF7F֖RB6WF֖VFRf'7BF6Pv26FfFVBFGvgW62rFBrF"f"FRCFVG2f"vЧFW6R֗FvFV7W&W2vW&RVVFVBs@FVG2S2RWW&V6VB&V7FvFFRf'7@rcBFVG2F2FVG2F"BrFVG2&FF2B2RFW&VgFW 6VRF6vRBF֖7G&F"ԆFvǖfW&cRbFVG2WW&V6VBgW6&V7Fw&FW2GW&rG&VFVBvFtd6&FvF&VFW7FRFR6FV6Pbw&FR2BgW6&V7F2v2R76PFR6FV6RbgW6&V7F2w&FW2v0SRRFVG2&V6Vfrtd6&FvF&VFW7FRvFw&FR2BgW6&V7F0&W'FVBRFVG2&V6Vfrtd6&FvF&VFW7FRFR6FV6R`gW6&V7F2v2vW7BF3R@w&GVǒFV7&V6VBF2"BR#RRrPBBR&W7V7FfVǒGW&r76R"FR6FV6RbgW6&V7F0v2#BRFVG2&V6Vfrtd6&FvF&VFW7FRBFV7&V6VBvF7V'6WVVB76W2GW&rtdFW&gW6&V7F2w&FW2vW&R'6W'fVBRbFVG2w&FP2BgW6&V7F2vW&R&W'FVBGW&rtdFW&fW&"RbFVG2WW&V6VBgW6&V7FVFrFF66FVFbtdWWG&V6&2ǖ7F2WVV֖FR6FV6RbWWG&V&W'FVB2W&666WGf"&FF6wVVWFp6WFV&W"#B( 2#r#p6FVv4FRSF5E$VVWFr7&VFW2f'Vf v&6&&F77VW2&FF6w