POLARIX Trial – Safety results
The majority of adverse reactions ≥10% were generally comparable across treatment arms1,*
*Adverse reactions with ≥5% difference in all grades or grade ≥3 include (POLIVY + R-CHP vs R-CHOP): diarrhea (all grades: 31% vs 20%; grade ≥3: 3.9% vs 1.8%), febrile neutropenia (all grades and grade ≥3: 15% vs 9%), and nausea (all grades: 42% vs 37%; grade ≥3: 1.1% vs 0.5%).
Most common adverse reactions in ≥20% of patients
- The rates of peripheral neuropathy between the POLIVY + R-CHP vs R-CHOP arms were 53% vs 54%, respectively1
- The rates of febrile neutropenia between the POLIVY + R-CHP vs R-CHOP arms were 15% and 9% respectively (for all grades and grade ≥ 3)1
- The rates of grade 3-4 infections were comparable between POLIVY + R-CHP vs R-CHOP arms (14% vs 11%)1
- Serious ARs occurred in 34% of patients who received POLIVY + R-CHP vs 30.6% of patients who received R-CHOP1,15
- Serious ARs in ≥5% of patients who received POLIVY + R-CHP included febrile neutropenia and pneumonia1
- Fatal ARs within 90 days of last treatment occurred in 3% of patients who received POLIVY + R-CHP vs 2.3% of patients who received R-CHOP. These were primarily from infection, including pneumonia (0.9% and 0.7%, respectively) and sepsis (0.2% and 0.7%, respectively) in the POLIVY + R-CHP vs R-CHOP arms1,2
- New or worsening Grade 3 to 4 laboratory abnormalities in ≥10% of patients were lymphopenia, neutropenia, hyperuricemia, and anemia1
Select adverse reactions occurring in ≥10% of patients treated with POLIVY + R-CHP in POLARIX1
Blood and lymphatic system disorders†
All Grades (%)
Grade 3-4 (%)
All Grades (%)
Grade 3-4 (%)
Lymphopenia
80
44
77
44
Anemia
68
14
67
11
Neutropenia
60
39
60
42
Thrombocytopenia
32
8
33
6
Febrile neutropenia‡
15
15
9
9
Investigations†
All Grades (%)
Grade 3-4 (%)
All Grades (%)
Grade 3-4 (%)
Creatinine increased
66
0.7
64
0.9
Aspartate aminotransferase increased
26
0.7
23
1.1
Alanine aminotransferase increased
25
1.4
27
0.5
Alkaline phosphatase increased
23
0
22
0.5
Uric acid increased
19
18
17
16
Weight decreased
13
0.9
12
0.2
Nervous system disorders
All Grades (%)
Grade 3-4 (%)
All Grades (%)
Grade 3-4 (%)
Peripheral neuropathy§,‖
53
1.6
54
1.1
Altered taste
14
0
16
0
Headache
13
0.2
14
0.9
Gastrointestinal disorders
All Grades (%)
Grade 3-4 (%)
All Grades (%)
Grade 3-4 (%)
Nausea
42
1.1
37
0.5
Diarrhea
31
3.9
20
1.8
Constipation
29
1.1
29
0.2
Mucositis¶
22
1.4
19
0.5
Abdominal pain#
16
1.1
14
1.6
Vomiting
15
1.1
14
0.7
General disorders
All Grades (%)
Grade 3-4 (%)
All Grades (%)
Grade 3-4 (%)
Fatigue
37
2.5
38
3.0
Pyrexia
16
1.4
13
0
Edema**
14
0.5
11
0.2
Infusion-related reaction††
13
1.1
16
1.6
Skin and subcutaneous tissue disorders
All Grades (%)
Grade 3-4 (%)
All Grades (%)
Grade 3-4 (%)
Alopecia
24
0
24
0.2
Rash‡‡
13
0.7
Musculoskeletal disorders
All Grades (%)
Grade 3-4 (%)
All Grades (%)
Grade 3-4 (%)
Musculoskeletal pain§§
19
0.5
21
1.8
Infections
All Grades (%)
Grade 3-4 (%)
All Grades (%)
Grade 3-4 (%)
Upper respiratory tract infection‖‖
17
0.5
16
0.5
Metabolism and nutrition disorders
All Grades (%)
Grade 3-4 (%)
All Grades (%)
Grade 3-4 (%)
Decreased Appetite
17
1.1
14
0.7
Respiratory disorders
All Grades (%)
Grade 3-4 (%)
All Grades (%)
Grade 3-4 (%)
Cough
15
0
14
0
Dyspnea
13
0.9
10
0.9
This table includes a combination of grouped and ungrouped terms. Events were graded using NCI CTCAE version 4.0.
†Laboratory values are based on integrated analysis of laboratory and adverse reaction data. Reported investigations exclude electrolytes.
‡Febrile neutropenia includes febrile neutropenia, febrile bone marrow aplasia, and neutropenic sepsis.
§At last assessment, peripheral neuropathy was unresolved in 42% in the POLIVY + R-CHP arm and in 33%in the R-CHOP arm.
‖Peripheral neuropathy includes all terms containing “neuropathy”, neuralgia, dysesthesia, paresthesia, hypoesthesia, peroneal nerve palsy, hypotonia, hyporeflexia, neuromyopathy, and hyperesthesia.
¶Mucositis includes stomatitis, oropharyngeal pain, mucosal inflammation, mouth ulceration, oral pain, oropharyngeal discomfort, aphthous ulcer, odynophagia, oral discomfort, tongue blistering, and tongue ulceration.
#Abdominal pain includes abdominal pain, abdominal discomfort, gastrointestinal pain, epigastric discomfort, and related terms.
**Edema includes edema, face edema, swelling face, edema peripheral, fluid overload, fluid retention, pulmonary edema, peripheral swelling, and swelling.
††Infusion related reaction is reflective of the combination regimen due to same-day administration.
‡‡Rash includes rash, dermatitis, and related terms.
§§Musculoskeletal pain includes musculoskeletal pain, back pain, musculoskeletal chest pain, neck pain, myalgia, and bone pain.
‖‖Upper respiratory tract infection includes sinusitis, laryngitis, pharyngitis, nasopharyngitis, rhinitis, and specific infections.
Other clinically relevant adverse reactions in <10% of patients who received POLIVY + R-CHP included pneumonia, herpesvirus infection, sepsis, cytomegalovirus infection, tumor lysis syndrome, renal insufficiency, and pneumonitis.
Dose reductions & discontinuation rates with POLIVY + R-CHP vs R-CHOP1,2
ARs leading to dose reduction
6%
10.3%
ARs leading to permanent discontinuation
4.4%
5%
ARs leading to dose interruption
18%
15.3%
More patients received 6 cycles of POLIVY vs vincristine (92% vs 89%)2
Drug interactions
Strong CYP3A inhibitors
- Concomitant use with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase POLIVY toxicities. Monitor patients for signs of toxicity
Strong CYP3A inducers
- Concomitant use with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC
AR = adverse reaction; AUC = area under the construction-time curve; CYP3A = cytochrome P450 family 3 subfamily A; NCI CTCAE = National Cancer Institute Common Terminology Criteria for Adverse Events.
References
- POLIVY, Israeli MoH approved prescribing information,Aug 2022
- Tilly H, Morschhauser F, Sehn LH, et al. Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. N Engl J Med. 2022;386(4):351-363.
Contact The Hematology Team
Roche Pharmaceuticals (Israel) Ltd.
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📞09-9737777
📧 israel.Hematology@roche.com