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LA JOLLA, CALIF. — Prolonged exposure to mogamulizumab can improve responses without compromising safety in patients with cutaneous T-cell lymphoma (CTCL), according to a post hoc analysis of the MAVORIC trial.
Investigators found that exposure to mogamulizumab correlated with response. The highest response rate — 75.6% — was observed in patients exposed to the drug for at least 351 days, and the lowest — 1.9% — was observed in patients exposed to mogamulizumab for less than 72 days.
On the other hand, rates of adverse events (AEs) were similar regardless of how long patients were treated with mogamulizumab.
Youn H. Kim, MD, of Stanford Cancer Institute at Stanford (Calif.) University, and her colleagues presented these findings at the annual T-cell Lymphoma Forum.
The phase 3 MAVORIC trial (NCT01728805) included 372 adults with CTCL who had failed at least one systemic therapy. The patients were randomized to treatment with mogamulizumab or vorinostat.
Results from this comparison were previously reported at the 10th annual T-cell Lymphoma Forum.
At this year’s meeting, Dr. Kim and her colleagues reported results in 184 patients who were randomized to mogamulizumab — 105 of whom had mycosis fungoides (MF) and 79 of whom had Sézary syndrome (SS).
Patients were exposed to mogamulizumab for a mean of 275.2 days and a median of 170.0 days (range, 1-1,617 days).
The investigators divided patients into the following quartiles according to mogamulizumab exposure:
- Less than 72 days — 52 patients (28%)
- 72-170 days — 40 patients (22%)
- 171-351 days — 47 patients (26%)
- More than 351 days — 45 patients (24%).
Patients exposed to mogamulizumab for longer were more likely to have SS, stage III/IV disease, blood involvement, and a performance status of 0.
Dr. Kim said the SS patients “benefited a lot” from mogamulizumab and therefore remained on treatment longer.
Response
As expected, patients exposed to mogamulizumab for the longest period had the highest global response rates. Confirmed response rates according to drug exposure were as follows:
- Less than 72 days: 1.9% overall, 0% for SS, and 2.9% for MF
- 72-170 days: 10% overall, 18.8% for SS, and 4.2% for MF
- 171-351 days: 29.8% overall, 36.4% for SS, and 24% for MF
- More than 351 days: 75.6% overall, 83.3% for SS, and 66.7% for MF.
In addition, rates of complete response (CR) and partial response (PR) tended to increase with mogamulizumab exposure. Rates of CR, PR, and stable disease (SD) according to exposure time were as follows:
- Less than 72 days: 0% CR, 7.7% PR, and 38.5% SD
- 72-170 days: 2.5% CR, 20% PR, and 62.5% SD
- 171-351 days: 2.1% CR, 34% PR, and 57.4% SD
- More than 351 days: 6.7% CR, 71.1% PR, and 17.8% SD.
Safety
“The percentage of patients reporting adverse events was not different in the long-term treatment-exposure patients, compared to the short-term,” Dr. Kim said.
Percentages of treatment-emergent AEs (TEAEs) and serious AEs (SAEs) according to mogamulizumab exposure were as follows:
- Less than 72 days: 26.6% TEAEs and 6.5% SAEs
- 72-170 days: 18.5% TEAEs and 3.3% SAEs
- 171-351 days: 23.4% TEAEs and 6.0% SAEs
- More than 351 days: 21.7% TEAEs and 4.3% SAEs.
“The majority of the grade 3 events occurred in the first two quartiles, not later, which is important to show,” Dr. Kim said.
Most grade 3 AEs occurred within 170 days of treatment initiation, and the median time to a grade 3 or higher AE was 109 days.
The most common treatment-related AEs in the longest exposure cohort were drug eruption (20.0%), thrombocytopenia (11.1%), stomatitis (8.9%), and anemia (8.9%).
Of all patients in this analysis, 45 experienced drug eruption, which was defined as a skin rash possibly, probably, or definitely related to the study drug.
Nine drug eruption events were grade 3, and the rest were grade 1 or 2. The median time to drug eruption was 107 days.
While drug eruption “didn’t show up early,” there is no cumulative risk with longer exposure to mogamulizumab, Dr. Kim said. Likewise, she said, autoimmune AEs were not dose-cumulative events.
There were two patients with definite autoimmune disease — a 65-year-old man with Miller Fisher syndrome (occurring 199 days after mogamulizumab initiation) and a 40-year-old woman with myositis (151 days) and myocarditis (310 days).
The investigators also identified three patients with possible autoimmune disease, including:
- Pneumonitis (310 days) in a 74-year-old woman
- Polymyalgia rheumatica (209 days) and myopathy (not available) in an 84-year-old man
- Hepatitis (144 days), pneumonitis (about 174 days), and polymyositis (about 174 days) in a 73-year-old man.
Dr. Kim and her colleagues said these data suggest prolonged treatment with mogamulizumab is not associated with an increased safety risk in patients with MF or SS. And the manageable safety profile of mogamulizumab meant that patients who derived a clinical benefit could remain on the drug for an extended period of time.
The MAVORIC trial was sponsored by Kyowa Hakko Kirin Pharma. Dr. Kim reported relationships with Merck, Portola Pharmaceuticals, Soligenix, Takeda, TetraLogic Pharmaceuticals, Kyowa Kirin, Seattle Genetics, Medivir, Neumedicines, Eisai, Innate Pharma, Galderma, Miragen Therapeutics, Forty Seven, and Horizon Pharma. Her coinvestigators reported relationships with several companies.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. — Prolonged exposure to mogamulizumab can improve responses without compromising safety in patients with cutaneous T-cell lymphoma (CTCL), according to a post hoc analysis of the MAVORIC trial.
Investigators found that exposure to mogamulizumab correlated with response. The highest response rate — 75.6% — was observed in patients exposed to the drug for at least 351 days, and the lowest — 1.9% — was observed in patients exposed to mogamulizumab for less than 72 days.
On the other hand, rates of adverse events (AEs) were similar regardless of how long patients were treated with mogamulizumab.
Youn H. Kim, MD, of Stanford Cancer Institute at Stanford (Calif.) University, and her colleagues presented these findings at the annual T-cell Lymphoma Forum.
The phase 3 MAVORIC trial (NCT01728805) included 372 adults with CTCL who had failed at least one systemic therapy. The patients were randomized to treatment with mogamulizumab or vorinostat.
Results from this comparison were previously reported at the 10th annual T-cell Lymphoma Forum.
At this year’s meeting, Dr. Kim and her colleagues reported results in 184 patients who were randomized to mogamulizumab — 105 of whom had mycosis fungoides (MF) and 79 of whom had Sézary syndrome (SS).
Patients were exposed to mogamulizumab for a mean of 275.2 days and a median of 170.0 days (range, 1-1,617 days).
The investigators divided patients into the following quartiles according to mogamulizumab exposure:
- Less than 72 days — 52 patients (28%)
- 72-170 days — 40 patients (22%)
- 171-351 days — 47 patients (26%)
- More than 351 days — 45 patients (24%).
Patients exposed to mogamulizumab for longer were more likely to have SS, stage III/IV disease, blood involvement, and a performance status of 0.
Dr. Kim said the SS patients “benefited a lot” from mogamulizumab and therefore remained on treatment longer.
Response
As expected, patients exposed to mogamulizumab for the longest period had the highest global response rates. Confirmed response rates according to drug exposure were as follows:
- Less than 72 days: 1.9% overall, 0% for SS, and 2.9% for MF
- 72-170 days: 10% overall, 18.8% for SS, and 4.2% for MF
- 171-351 days: 29.8% overall, 36.4% for SS, and 24% for MF
- More than 351 days: 75.6% overall, 83.3% for SS, and 66.7% for MF.
In addition, rates of complete response (CR) and partial response (PR) tended to increase with mogamulizumab exposure. Rates of CR, PR, and stable disease (SD) according to exposure time were as follows:
- Less than 72 days: 0% CR, 7.7% PR, and 38.5% SD
- 72-170 days: 2.5% CR, 20% PR, and 62.5% SD
- 171-351 days: 2.1% CR, 34% PR, and 57.4% SD
- More than 351 days: 6.7% CR, 71.1% PR, and 17.8% SD.
Safety
“The percentage of patients reporting adverse events was not different in the long-term treatment-exposure patients, compared to the short-term,” Dr. Kim said.
Percentages of treatment-emergent AEs (TEAEs) and serious AEs (SAEs) according to mogamulizumab exposure were as follows:
- Less than 72 days: 26.6% TEAEs and 6.5% SAEs
- 72-170 days: 18.5% TEAEs and 3.3% SAEs
- 171-351 days: 23.4% TEAEs and 6.0% SAEs
- More than 351 days: 21.7% TEAEs and 4.3% SAEs.
“The majority of the grade 3 events occurred in the first two quartiles, not later, which is important to show,” Dr. Kim said.
Most grade 3 AEs occurred within 170 days of treatment initiation, and the median time to a grade 3 or higher AE was 109 days.
The most common treatment-related AEs in the longest exposure cohort were drug eruption (20.0%), thrombocytopenia (11.1%), stomatitis (8.9%), and anemia (8.9%).
Of all patients in this analysis, 45 experienced drug eruption, which was defined as a skin rash possibly, probably, or definitely related to the study drug.
Nine drug eruption events were grade 3, and the rest were grade 1 or 2. The median time to drug eruption was 107 days.
While drug eruption “didn’t show up early,” there is no cumulative risk with longer exposure to mogamulizumab, Dr. Kim said. Likewise, she said, autoimmune AEs were not dose-cumulative events.
There were two patients with definite autoimmune disease — a 65-year-old man with Miller Fisher syndrome (occurring 199 days after mogamulizumab initiation) and a 40-year-old woman with myositis (151 days) and myocarditis (310 days).
The investigators also identified three patients with possible autoimmune disease, including:
- Pneumonitis (310 days) in a 74-year-old woman
- Polymyalgia rheumatica (209 days) and myopathy (not available) in an 84-year-old man
- Hepatitis (144 days), pneumonitis (about 174 days), and polymyositis (about 174 days) in a 73-year-old man.
Dr. Kim and her colleagues said these data suggest prolonged treatment with mogamulizumab is not associated with an increased safety risk in patients with MF or SS. And the manageable safety profile of mogamulizumab meant that patients who derived a clinical benefit could remain on the drug for an extended period of time.
The MAVORIC trial was sponsored by Kyowa Hakko Kirin Pharma. Dr. Kim reported relationships with Merck, Portola Pharmaceuticals, Soligenix, Takeda, TetraLogic Pharmaceuticals, Kyowa Kirin, Seattle Genetics, Medivir, Neumedicines, Eisai, Innate Pharma, Galderma, Miragen Therapeutics, Forty Seven, and Horizon Pharma. Her coinvestigators reported relationships with several companies.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. — Prolonged exposure to mogamulizumab can improve responses without compromising safety in patients with cutaneous T-cell lymphoma (CTCL), according to a post hoc analysis of the MAVORIC trial.
Investigators found that exposure to mogamulizumab correlated with response. The highest response rate — 75.6% — was observed in patients exposed to the drug for at least 351 days, and the lowest — 1.9% — was observed in patients exposed to mogamulizumab for less than 72 days.
On the other hand, rates of adverse events (AEs) were similar regardless of how long patients were treated with mogamulizumab.
Youn H. Kim, MD, of Stanford Cancer Institute at Stanford (Calif.) University, and her colleagues presented these findings at the annual T-cell Lymphoma Forum.
The phase 3 MAVORIC trial (NCT01728805) included 372 adults with CTCL who had failed at least one systemic therapy. The patients were randomized to treatment with mogamulizumab or vorinostat.
Results from this comparison were previously reported at the 10th annual T-cell Lymphoma Forum.
At this year’s meeting, Dr. Kim and her colleagues reported results in 184 patients who were randomized to mogamulizumab — 105 of whom had mycosis fungoides (MF) and 79 of whom had Sézary syndrome (SS).
Patients were exposed to mogamulizumab for a mean of 275.2 days and a median of 170.0 days (range, 1-1,617 days).
The investigators divided patients into the following quartiles according to mogamulizumab exposure:
- Less than 72 days — 52 patients (28%)
- 72-170 days — 40 patients (22%)
- 171-351 days — 47 patients (26%)
- More than 351 days — 45 patients (24%).
Patients exposed to mogamulizumab for longer were more likely to have SS, stage III/IV disease, blood involvement, and a performance status of 0.
Dr. Kim said the SS patients “benefited a lot” from mogamulizumab and therefore remained on treatment longer.
Response
As expected, patients exposed to mogamulizumab for the longest period had the highest global response rates. Confirmed response rates according to drug exposure were as follows:
- Less than 72 days: 1.9% overall, 0% for SS, and 2.9% for MF
- 72-170 days: 10% overall, 18.8% for SS, and 4.2% for MF
- 171-351 days: 29.8% overall, 36.4% for SS, and 24% for MF
- More than 351 days: 75.6% overall, 83.3% for SS, and 66.7% for MF.
In addition, rates of complete response (CR) and partial response (PR) tended to increase with mogamulizumab exposure. Rates of CR, PR, and stable disease (SD) according to exposure time were as follows:
- Less than 72 days: 0% CR, 7.7% PR, and 38.5% SD
- 72-170 days: 2.5% CR, 20% PR, and 62.5% SD
- 171-351 days: 2.1% CR, 34% PR, and 57.4% SD
- More than 351 days: 6.7% CR, 71.1% PR, and 17.8% SD.
Safety
“The percentage of patients reporting adverse events was not different in the long-term treatment-exposure patients, compared to the short-term,” Dr. Kim said.
Percentages of treatment-emergent AEs (TEAEs) and serious AEs (SAEs) according to mogamulizumab exposure were as follows:
- Less than 72 days: 26.6% TEAEs and 6.5% SAEs
- 72-170 days: 18.5% TEAEs and 3.3% SAEs
- 171-351 days: 23.4% TEAEs and 6.0% SAEs
- More than 351 days: 21.7% TEAEs and 4.3% SAEs.
“The majority of the grade 3 events occurred in the first two quartiles, not later, which is important to show,” Dr. Kim said.
Most grade 3 AEs occurred within 170 days of treatment initiation, and the median time to a grade 3 or higher AE was 109 days.
The most common treatment-related AEs in the longest exposure cohort were drug eruption (20.0%), thrombocytopenia (11.1%), stomatitis (8.9%), and anemia (8.9%).
Of all patients in this analysis, 45 experienced drug eruption, which was defined as a skin rash possibly, probably, or definitely related to the study drug.
Nine drug eruption events were grade 3, and the rest were grade 1 or 2. The median time to drug eruption was 107 days.
While drug eruption “didn’t show up early,” there is no cumulative risk with longer exposure to mogamulizumab, Dr. Kim said. Likewise, she said, autoimmune AEs were not dose-cumulative events.
There were two patients with definite autoimmune disease — a 65-year-old man with Miller Fisher syndrome (occurring 199 days after mogamulizumab initiation) and a 40-year-old woman with myositis (151 days) and myocarditis (310 days).
The investigators also identified three patients with possible autoimmune disease, including:
- Pneumonitis (310 days) in a 74-year-old woman
- Polymyalgia rheumatica (209 days) and myopathy (not available) in an 84-year-old man
- Hepatitis (144 days), pneumonitis (about 174 days), and polymyositis (about 174 days) in a 73-year-old man.
Dr. Kim and her colleagues said these data suggest prolonged treatment with mogamulizumab is not associated with an increased safety risk in patients with MF or SS. And the manageable safety profile of mogamulizumab meant that patients who derived a clinical benefit could remain on the drug for an extended period of time.
The MAVORIC trial was sponsored by Kyowa Hakko Kirin Pharma. Dr. Kim reported relationships with Merck, Portola Pharmaceuticals, Soligenix, Takeda, TetraLogic Pharmaceuticals, Kyowa Kirin, Seattle Genetics, Medivir, Neumedicines, Eisai, Innate Pharma, Galderma, Miragen Therapeutics, Forty Seven, and Horizon Pharma. Her coinvestigators reported relationships with several companies.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
REPORTING FROM TCLF 2019
Key clinical point:
Major finding: The highest response rate – 75.6% – was observed in patients exposed to mogamulizumab for at least 351 days.
Study details: A post hoc analysis of the MAVORIC trial, including 184 patients treated with mogamulizumab.
Disclosures: The MAVORIC trial was sponsored by Kyowa Hakko Kirin Pharma. Investigators disclosed relationships with several companies.