Chemo-free triplet produces ‘favorable’ results in advanced disease

Mantle cell lymphoma

LUGANO, SWITZERLAND—A chemotherapy-free combination regimen has demonstrated “favorable” safety and efficacy in patients with advanced chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and non-Hodgkin lymphoma (NHL), according to researchers.

They found that treatment with ublituximab, umbralisib, and ibrutinib produced responses in patients with CLL/SLL, marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL).

Many of these patients are still receiving the combination, some of them beyond 1 year, said Lorretta Nastoupil, MD, of MD Anderson Cancer Center in Houston, Texas.

She presented results with the treatment at the 14th International Conference on Malignant Lymphoma (ICML).

The research was sponsored by TG Therapeutics, the company developing ublituximab (TG-1101) and umbralisib (TGR-1202).

Patients and treatment

Dr Nastoupil presented data on 38 patients—20 with CLL/SLL, and 18 with NHL. Three of the CLL/SLL patients were treatment-naïve. The rest had relapsed/refractory disease.

All NHL patients had relapsed/refractory disease—6 with DLBCL, 6 with FL, 4 with MCL, and 2 with MZL.

For the entire cohort, the median age was 65 (range, 32-85), and most patients (n=29) were male. They had received a median of 3 prior treatment regimens (range, 0-6).

In this trial, the patients received:

• Ublituximab at 900 mg
• Ibrutinib at 420 mg (CLL/SLL) or 560 mg (NHL)
• Umbralisib at 400 mg, 600 mg, or 800 mg.

Eighty-one percent of patients have been on study for more than 6 months. The median time on study is 11.1 months (range, 0.4 to 30+ months).

Safety

There was 1 dose-limiting toxicity in the CLL cohort (umbralisib at 400 mg)—reactivated varicella zoster. And 2 patients discontinued treatment due to an adverse event (AE)—1 due to sepsis and 1 due to pneumonia.

Neutropenia (18%) and pneumonia (11%) were the only grade 3/4 AEs that occurred in more than 10% of patients. Other grade 3/4 AEs included thrombocytopenia (8%), diarrhea (3%), dizziness (3%), pyrexia (3%), rash (3%), anemia (3%), dyspnea (3%), and stomatitis (3%).

The most common AEs of any grade were diarrhea (47%), fatigue (47%), dizziness (37%), insomnia (34%), nausea (34%), neutropenia (32%), cough (32%), and infusion-related reactions (32%).

Efficacy

Thirty-six patients were evaluable for efficacy—19 with CLL/SLL and 17 with NHL patients. Two patients discontinued treatment before the first efficacy assessment—1 due to pneumonia and 1 at investigator discretion.

For the entire cohort, the overall response rate (ORR) was 83%.

In the CLL/SLL cohort, the ORR was 100% (19/19), and the complete response (CR) rate was 32% (n=6). However, 4 of the 6 CRs are pending bone marrow confirmation.

Dr Nastoupil noted that 8 of the CLL patients had a 17p and/or 11q deletion, and 3 had previously received treatment with a BTK and/or PI3Kδ inhibitor.

One patient who was refractory to both idelalisib and ibrutinib achieved a CR with the triplet regimen, and this response has been ongoing for more than 1.5 years.

Among patients with NHL, the ORR was 100% in patients with MZL (2/2) and MCL (4/4). The ORR was 80% (4/5) in FL patients, and 17% (1/6) in DLBCL patients.

The CR rate was 50% in patients with MZL (1/2) and MCL (2/4) and 20% in patients with FL (1/5).

Dr Nastoupil pointed out that the FL patients were heavily pretreated. Two of them had received an autologous stem cell transplant, 1 was refractory to prior ibrutinib treatment, and 1 had received 5 prior lines of rituximab-based therapy.

She also noted that the DLBCL patients had a median of 4 prior therapies, and 4 of these patients had non-GCB DLBCL, including the only patient who responded to the triplet.

“[T]he combination of ublituximab, umbralisib, and ibrutinib in advanced CLL and NHL demonstrated a favorable toxicity profile as well as favorable efficacy,” Dr Nastoupil said in closing.

“[This] suggests umbralisib may be safely combined with other targeted agents to overcome mechanisms of resistance.” 

Mantle cell lymphoma

LUGANO, SWITZERLAND—A chemotherapy-free combination regimen has demonstrated “favorable” safety and efficacy in patients with advanced chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and non-Hodgkin lymphoma (NHL), according to researchers.

They found that treatment with ublituximab, umbralisib, and ibrutinib produced responses in patients with CLL/SLL, marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL).

Many of these patients are still receiving the combination, some of them beyond 1 year, said Lorretta Nastoupil, MD, of MD Anderson Cancer Center in Houston, Texas.

She presented results with the treatment at the 14th International Conference on Malignant Lymphoma (ICML).

The research was sponsored by TG Therapeutics, the company developing ublituximab (TG-1101) and umbralisib (TGR-1202).

Patients and treatment

Dr Nastoupil presented data on 38 patients—20 with CLL/SLL, and 18 with NHL. Three of the CLL/SLL patients were treatment-naïve. The rest had relapsed/refractory disease.

All NHL patients had relapsed/refractory disease—6 with DLBCL, 6 with FL, 4 with MCL, and 2 with MZL.

For the entire cohort, the median age was 65 (range, 32-85), and most patients (n=29) were male. They had received a median of 3 prior treatment regimens (range, 0-6).

In this trial, the patients received:

• Ublituximab at 900 mg
• Ibrutinib at 420 mg (CLL/SLL) or 560 mg (NHL)
• Umbralisib at 400 mg, 600 mg, or 800 mg.

Eighty-one percent of patients have been on study for more than 6 months. The median time on study is 11.1 months (range, 0.4 to 30+ months).

Safety

There was 1 dose-limiting toxicity in the CLL cohort (umbralisib at 400 mg)—reactivated varicella zoster. And 2 patients discontinued treatment due to an adverse event (AE)—1 due to sepsis and 1 due to pneumonia.

Neutropenia (18%) and pneumonia (11%) were the only grade 3/4 AEs that occurred in more than 10% of patients. Other grade 3/4 AEs included thrombocytopenia (8%), diarrhea (3%), dizziness (3%), pyrexia (3%), rash (3%), anemia (3%), dyspnea (3%), and stomatitis (3%).

The most common AEs of any grade were diarrhea (47%), fatigue (47%), dizziness (37%), insomnia (34%), nausea (34%), neutropenia (32%), cough (32%), and infusion-related reactions (32%).

Efficacy

Thirty-six patients were evaluable for efficacy—19 with CLL/SLL and 17 with NHL patients. Two patients discontinued treatment before the first efficacy assessment—1 due to pneumonia and 1 at investigator discretion.

For the entire cohort, the overall response rate (ORR) was 83%.

In the CLL/SLL cohort, the ORR was 100% (19/19), and the complete response (CR) rate was 32% (n=6). However, 4 of the 6 CRs are pending bone marrow confirmation.

Dr Nastoupil noted that 8 of the CLL patients had a 17p and/or 11q deletion, and 3 had previously received treatment with a BTK and/or PI3Kδ inhibitor.

One patient who was refractory to both idelalisib and ibrutinib achieved a CR with the triplet regimen, and this response has been ongoing for more than 1.5 years.

Among patients with NHL, the ORR was 100% in patients with MZL (2/2) and MCL (4/4). The ORR was 80% (4/5) in FL patients, and 17% (1/6) in DLBCL patients.

The CR rate was 50% in patients with MZL (1/2) and MCL (2/4) and 20% in patients with FL (1/5).

Dr Nastoupil pointed out that the FL patients were heavily pretreated. Two of them had received an autologous stem cell transplant, 1 was refractory to prior ibrutinib treatment, and 1 had received 5 prior lines of rituximab-based therapy.

She also noted that the DLBCL patients had a median of 4 prior therapies, and 4 of these patients had non-GCB DLBCL, including the only patient who responded to the triplet.

“[T]he combination of ublituximab, umbralisib, and ibrutinib in advanced CLL and NHL demonstrated a favorable toxicity profile as well as favorable efficacy,” Dr Nastoupil said in closing.

“[This] suggests umbralisib may be safely combined with other targeted agents to overcome mechanisms of resistance.” 

Mantle cell lymphoma

LUGANO, SWITZERLAND—A chemotherapy-free combination regimen has demonstrated “favorable” safety and efficacy in patients with advanced chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and non-Hodgkin lymphoma (NHL), according to researchers.

They found that treatment with ublituximab, umbralisib, and ibrutinib produced responses in patients with CLL/SLL, marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL).

Many of these patients are still receiving the combination, some of them beyond 1 year, said Lorretta Nastoupil, MD, of MD Anderson Cancer Center in Houston, Texas.

She presented results with the treatment at the 14th International Conference on Malignant Lymphoma (ICML).

The research was sponsored by TG Therapeutics, the company developing ublituximab (TG-1101) and umbralisib (TGR-1202).

Patients and treatment

Dr Nastoupil presented data on 38 patients—20 with CLL/SLL, and 18 with NHL. Three of the CLL/SLL patients were treatment-naïve. The rest had relapsed/refractory disease.

All NHL patients had relapsed/refractory disease—6 with DLBCL, 6 with FL, 4 with MCL, and 2 with MZL.

For the entire cohort, the median age was 65 (range, 32-85), and most patients (n=29) were male. They had received a median of 3 prior treatment regimens (range, 0-6).

In this trial, the patients received:

• Ublituximab at 900 mg
• Ibrutinib at 420 mg (CLL/SLL) or 560 mg (NHL)
• Umbralisib at 400 mg, 600 mg, or 800 mg.

Eighty-one percent of patients have been on study for more than 6 months. The median time on study is 11.1 months (range, 0.4 to 30+ months).

Safety

There was 1 dose-limiting toxicity in the CLL cohort (umbralisib at 400 mg)—reactivated varicella zoster. And 2 patients discontinued treatment due to an adverse event (AE)—1 due to sepsis and 1 due to pneumonia.

Neutropenia (18%) and pneumonia (11%) were the only grade 3/4 AEs that occurred in more than 10% of patients. Other grade 3/4 AEs included thrombocytopenia (8%), diarrhea (3%), dizziness (3%), pyrexia (3%), rash (3%), anemia (3%), dyspnea (3%), and stomatitis (3%).

The most common AEs of any grade were diarrhea (47%), fatigue (47%), dizziness (37%), insomnia (34%), nausea (34%), neutropenia (32%), cough (32%), and infusion-related reactions (32%).

Efficacy

Thirty-six patients were evaluable for efficacy—19 with CLL/SLL and 17 with NHL patients. Two patients discontinued treatment before the first efficacy assessment—1 due to pneumonia and 1 at investigator discretion.

For the entire cohort, the overall response rate (ORR) was 83%.

In the CLL/SLL cohort, the ORR was 100% (19/19), and the complete response (CR) rate was 32% (n=6). However, 4 of the 6 CRs are pending bone marrow confirmation.

Dr Nastoupil noted that 8 of the CLL patients had a 17p and/or 11q deletion, and 3 had previously received treatment with a BTK and/or PI3Kδ inhibitor.

One patient who was refractory to both idelalisib and ibrutinib achieved a CR with the triplet regimen, and this response has been ongoing for more than 1.5 years.

Among patients with NHL, the ORR was 100% in patients with MZL (2/2) and MCL (4/4). The ORR was 80% (4/5) in FL patients, and 17% (1/6) in DLBCL patients.

The CR rate was 50% in patients with MZL (1/2) and MCL (2/4) and 20% in patients with FL (1/5).

Dr Nastoupil pointed out that the FL patients were heavily pretreated. Two of them had received an autologous stem cell transplant, 1 was refractory to prior ibrutinib treatment, and 1 had received 5 prior lines of rituximab-based therapy.

She also noted that the DLBCL patients had a median of 4 prior therapies, and 4 of these patients had non-GCB DLBCL, including the only patient who responded to the triplet.

“[T]he combination of ublituximab, umbralisib, and ibrutinib in advanced CLL and NHL demonstrated a favorable toxicity profile as well as favorable efficacy,” Dr Nastoupil said in closing.

“[This] suggests umbralisib may be safely combined with other targeted agents to overcome mechanisms of resistance.”