Lymphoma & Plasma Cell Disorders

For a group of clinicians in Australia, the diagnosis of meningococcal arthritis was “straightforward” except for abnormal serum total protein, anemia, and immunoglobulin results, which suggested their patient might have a hematological disorder such as myeloma.

The patient came to the hospital after 4 days of worsening knee and arm pain so severe he could not stand. His knees and both wrists showed swelling but no palpable lymphadenopathy or hepatosplenomegaly. The patient’s medical history showed he was taking no regular medications.

Joint aspiration grew Neisseria meningitidis. The patient’s blood tests showed hemoglobin 126 g/dL, white blood cell count 15.3 x 10⁹/L, an unusually high total protein level (100 g/L), and an IgM kappa paraprotein band of 45 g/L on protein electrophoresis. A computed tomography scan showed widespread lymphadenopathy, hepatosplenomegaly, and multilevel thoracic vertebral collapse. A bone marrow biopsy showed evidence of a lymphocytic infiltrate, with lymphoplasmacytoid differentiation.

The histology best fitted a diagnosis of nodal marginal zone lymphoma with plasmacytic differentiation, the clinicians say. Having ruled out other possibilities, they settled on non-Hodgkin lymphoma.

Initially, the suspicion was that the patient had septic arthritis due to Staphylococcus aureus (the most common organism isolated in septic arthritis), and he was given piperacillin/tazobactam. That was changed to flucloxacillin and then to ceftriaxone after the result of N meningitidis. The patient also was treated with rituximab and bendamustine for the lymphoma with a complete remission.

Meningococcal infection presenting as septic arthritis in the case of invasive meningococcemia is rare, the clinicians say, but primary meningococcal arthritis is even rarer. The case highlights the important aspect that “diagnosis of one condition can lead to diagnosis of another”—in this case, the lymphoma-weakened immune system led to the symptoms of polyarthropathy and the diagnosis of primary meningococcal arthritis. The clinicians also cited a case of a patient who presented with meningococcal meningitis and arthritis who was found to have an underlying Waldenström disease, and a patient whose HIV was diagnosed again after the patient presented with meningococcal arthritis symptoms.

The clinicans say such cases underscore the importance of screening for an underlying impaired immune response in patients presenting with rare conditions such as meningococcal arthritis.

For a group of clinicians in Australia, the diagnosis of meningococcal arthritis was “straightforward” except for abnormal serum total protein, anemia, and immunoglobulin results, which suggested their patient might have a hematological disorder such as myeloma.

The patient came to the hospital after 4 days of worsening knee and arm pain so severe he could not stand. His knees and both wrists showed swelling but no palpable lymphadenopathy or hepatosplenomegaly. The patient’s medical history showed he was taking no regular medications.

Joint aspiration grew Neisseria meningitidis. The patient’s blood tests showed hemoglobin 126 g/dL, white blood cell count 15.3 x 10⁹/L, an unusually high total protein level (100 g/L), and an IgM kappa paraprotein band of 45 g/L on protein electrophoresis. A computed tomography scan showed widespread lymphadenopathy, hepatosplenomegaly, and multilevel thoracic vertebral collapse. A bone marrow biopsy showed evidence of a lymphocytic infiltrate, with lymphoplasmacytoid differentiation.

The histology best fitted a diagnosis of nodal marginal zone lymphoma with plasmacytic differentiation, the clinicians say. Having ruled out other possibilities, they settled on non-Hodgkin lymphoma.

Initially, the suspicion was that the patient had septic arthritis due to Staphylococcus aureus (the most common organism isolated in septic arthritis), and he was given piperacillin/tazobactam. That was changed to flucloxacillin and then to ceftriaxone after the result of N meningitidis. The patient also was treated with rituximab and bendamustine for the lymphoma with a complete remission.

Meningococcal infection presenting as septic arthritis in the case of invasive meningococcemia is rare, the clinicians say, but primary meningococcal arthritis is even rarer. The case highlights the important aspect that “diagnosis of one condition can lead to diagnosis of another”—in this case, the lymphoma-weakened immune system led to the symptoms of polyarthropathy and the diagnosis of primary meningococcal arthritis. The clinicians also cited a case of a patient who presented with meningococcal meningitis and arthritis who was found to have an underlying Waldenström disease, and a patient whose HIV was diagnosed again after the patient presented with meningococcal arthritis symptoms.

The clinicans say such cases underscore the importance of screening for an underlying impaired immune response in patients presenting with rare conditions such as meningococcal arthritis.

For a group of clinicians in Australia, the diagnosis of meningococcal arthritis was “straightforward” except for abnormal serum total protein, anemia, and immunoglobulin results, which suggested their patient might have a hematological disorder such as myeloma.

The patient came to the hospital after 4 days of worsening knee and arm pain so severe he could not stand. His knees and both wrists showed swelling but no palpable lymphadenopathy or hepatosplenomegaly. The patient’s medical history showed he was taking no regular medications.

Joint aspiration grew Neisseria meningitidis. The patient’s blood tests showed hemoglobin 126 g/dL, white blood cell count 15.3 x 10⁹/L, an unusually high total protein level (100 g/L), and an IgM kappa paraprotein band of 45 g/L on protein electrophoresis. A computed tomography scan showed widespread lymphadenopathy, hepatosplenomegaly, and multilevel thoracic vertebral collapse. A bone marrow biopsy showed evidence of a lymphocytic infiltrate, with lymphoplasmacytoid differentiation.

The histology best fitted a diagnosis of nodal marginal zone lymphoma with plasmacytic differentiation, the clinicians say. Having ruled out other possibilities, they settled on non-Hodgkin lymphoma.

Initially, the suspicion was that the patient had septic arthritis due to Staphylococcus aureus (the most common organism isolated in septic arthritis), and he was given piperacillin/tazobactam. That was changed to flucloxacillin and then to ceftriaxone after the result of N meningitidis. The patient also was treated with rituximab and bendamustine for the lymphoma with a complete remission.

Meningococcal infection presenting as septic arthritis in the case of invasive meningococcemia is rare, the clinicians say, but primary meningococcal arthritis is even rarer. The case highlights the important aspect that “diagnosis of one condition can lead to diagnosis of another”—in this case, the lymphoma-weakened immune system led to the symptoms of polyarthropathy and the diagnosis of primary meningococcal arthritis. The clinicians also cited a case of a patient who presented with meningococcal meningitis and arthritis who was found to have an underlying Waldenström disease, and a patient whose HIV was diagnosed again after the patient presented with meningococcal arthritis symptoms.

The clinicans say such cases underscore the importance of screening for an underlying impaired immune response in patients presenting with rare conditions such as meningococcal arthritis.

Photo by Larry Young

LA JOLLA, CA—Results of a phase 2 study suggest chidamide can produce durable responses in patients with relapsed/refractory natural killer/T-cell lymphoma (NKTCL).

The overall response rate was 57.2% in these patients, and the complete response (CR) rate was 28.6%.

Seven of 14 evaluable patients were still receiving chidamide and still in response at last follow-up. For one patient, this was 50 weeks from initiating treatment with chidamide.

“The response is quite promising and encouraging,” said study investigator Huiqiang Huang, MD, PhD, of Sun Yat-sen University Cancer Center in Guangzhou, China.

“In terms of safety, the toxicity is mild to moderate.”

Dr Huang presented these results at the 10th Annual T-cell Lymphoma Forum.

This investigator-sponsored trial enrolled patients with relapsed/refractory non-Hodgkin lymphoma, but Dr Huang presented results in NKTCL patients only.

There were 15 NKTCL patients, most of whom were male (n=12). Their median age was 41 (range, 17-65). All 15 had an ECOG status of 0 or 1, 9 had stage I/II disease, and 6 had B symptoms.

Nine patients had Epstein-Barr virus (EBV) DNA levels of at least 1000 copy/mL at baseline, and 5 patients had lactate dehydrogenase levels of at least 245 U/L.

The patients had a median of 2 prior systemic therapies (range, 1-3), and 2 patients had undergone a transplant.

Efficacy

Patients received chidamide at 2 doses—10 mg daily or 30 mg twice a week. Dr Huang said both doses were effective against the lymphoma types studied, but the 30 mg twice-weekly dose appeared to be more effective for patients with NKTCL.

Fourteen NKTCL patients were evaluable for efficacy, and the median follow-up was 17.6 weeks (range, 2.6-50).

The overall response rate was 68.2% (6/14), and the CR rate was 28.6% (4/14). The disease control rate was 71.4%, meaning 10 of 14 patients had a CR, partial response (PR), or stable disease (SD).

Dr Huang noted that response was associated with elevated H3 acetylation level.

The median time to response was 5.25 weeks (range, 1.1-6.6).

As for duration of response, the 4 complete responders were still on treatment and in CR at last follow-up, which was 22.7 weeks, 38.1 weeks, 41.3 weeks, and 50 weeks, respectively, from treatment initiation.

Three of the 4 partial responders were still on treatment and in PR at 14.1 weeks, 26.9 weeks, and 32 weeks, respectively. Two patients with SD were still on treatment and in SD at 15.3 weeks and 15.9 weeks, respectively.

Three patients progressed while on treatment and died. A fourth patient died 2.6 weeks after treatment initiation.

Safety

Dr Huang noted that adverse events (AEs) were similar with the 2 dose groups. However, patients who received 30 mg biweekly had a higher incidence of gastrointestinal AEs.

Overall, the most common AEs were hematologic—anemia, thrombocytopenia, etc.—but dose reductions allowed for quick resolution of these AEs, according to Dr Huang.

AEs included:

• Lymphopenia—10 grade 1/2 and 1 grade 3/4
• Anemia—9 grade 1/2 and 3 grade 3/4
• Thrombocytopenia—7 grade 1/2 and grade 3/4
• Leukopenia—7 grade 1/2 and 6 grade 3/4
• Increased alanine aminotransferase—7 grade 1/2
• Neutropenia—6 grade 1/2 and 7 grade 3/4
• Increased aspartate aminotransferase—5 grade 1/2
• Hypoalbuminemia—4 grade 1/2
• Nausea—4 grade 1/2 and 1 grade 3/4
• Vomiting—3 grade 1/2
• Mucositis—2 grade 1/2
• Fatigue—2 grade 1/2
• Epistaxis—2 grade 1/2
• Abdominal distension—1 grade 1/2
• Loss of appetite—1 grade 1/2
• Diarrhea—1 grade 1/2
• Hyperbilirubinemia—1 grade 1/2
• Fever—1 grade 1/2 and grade 3/4
• Pain—1 grade 1/2
• Cough—1 grade 1/2
• Constipation—1 grade 1/2.

Dr Huang said EBV reactivation was not confirmed in this study. An elevated EBV DNA load was only observed in 2 patients with progressive disease.

Photo by Larry Young

LA JOLLA, CA—Results of a phase 2 study suggest chidamide can produce durable responses in patients with relapsed/refractory natural killer/T-cell lymphoma (NKTCL).

The overall response rate was 57.2% in these patients, and the complete response (CR) rate was 28.6%.

Seven of 14 evaluable patients were still receiving chidamide and still in response at last follow-up. For one patient, this was 50 weeks from initiating treatment with chidamide.

“The response is quite promising and encouraging,” said study investigator Huiqiang Huang, MD, PhD, of Sun Yat-sen University Cancer Center in Guangzhou, China.

“In terms of safety, the toxicity is mild to moderate.”

Dr Huang presented these results at the 10th Annual T-cell Lymphoma Forum.

This investigator-sponsored trial enrolled patients with relapsed/refractory non-Hodgkin lymphoma, but Dr Huang presented results in NKTCL patients only.

There were 15 NKTCL patients, most of whom were male (n=12). Their median age was 41 (range, 17-65). All 15 had an ECOG status of 0 or 1, 9 had stage I/II disease, and 6 had B symptoms.

Nine patients had Epstein-Barr virus (EBV) DNA levels of at least 1000 copy/mL at baseline, and 5 patients had lactate dehydrogenase levels of at least 245 U/L.

The patients had a median of 2 prior systemic therapies (range, 1-3), and 2 patients had undergone a transplant.

Efficacy

Patients received chidamide at 2 doses—10 mg daily or 30 mg twice a week. Dr Huang said both doses were effective against the lymphoma types studied, but the 30 mg twice-weekly dose appeared to be more effective for patients with NKTCL.

Fourteen NKTCL patients were evaluable for efficacy, and the median follow-up was 17.6 weeks (range, 2.6-50).

The overall response rate was 68.2% (6/14), and the CR rate was 28.6% (4/14). The disease control rate was 71.4%, meaning 10 of 14 patients had a CR, partial response (PR), or stable disease (SD).

Dr Huang noted that response was associated with elevated H3 acetylation level.

The median time to response was 5.25 weeks (range, 1.1-6.6).

As for duration of response, the 4 complete responders were still on treatment and in CR at last follow-up, which was 22.7 weeks, 38.1 weeks, 41.3 weeks, and 50 weeks, respectively, from treatment initiation.

Three of the 4 partial responders were still on treatment and in PR at 14.1 weeks, 26.9 weeks, and 32 weeks, respectively. Two patients with SD were still on treatment and in SD at 15.3 weeks and 15.9 weeks, respectively.

Three patients progressed while on treatment and died. A fourth patient died 2.6 weeks after treatment initiation.

Safety

Dr Huang noted that adverse events (AEs) were similar with the 2 dose groups. However, patients who received 30 mg biweekly had a higher incidence of gastrointestinal AEs.

Overall, the most common AEs were hematologic—anemia, thrombocytopenia, etc.—but dose reductions allowed for quick resolution of these AEs, according to Dr Huang.

AEs included:

• Lymphopenia—10 grade 1/2 and 1 grade 3/4
• Anemia—9 grade 1/2 and 3 grade 3/4
• Thrombocytopenia—7 grade 1/2 and grade 3/4
• Leukopenia—7 grade 1/2 and 6 grade 3/4
• Increased alanine aminotransferase—7 grade 1/2
• Neutropenia—6 grade 1/2 and 7 grade 3/4
• Increased aspartate aminotransferase—5 grade 1/2
• Hypoalbuminemia—4 grade 1/2
• Nausea—4 grade 1/2 and 1 grade 3/4
• Vomiting—3 grade 1/2
• Mucositis—2 grade 1/2
• Fatigue—2 grade 1/2
• Epistaxis—2 grade 1/2
• Abdominal distension—1 grade 1/2
• Loss of appetite—1 grade 1/2
• Diarrhea—1 grade 1/2
• Hyperbilirubinemia—1 grade 1/2
• Fever—1 grade 1/2 and grade 3/4
• Pain—1 grade 1/2
• Cough—1 grade 1/2
• Constipation—1 grade 1/2.

Dr Huang said EBV reactivation was not confirmed in this study. An elevated EBV DNA load was only observed in 2 patients with progressive disease.

Photo by Larry Young

LA JOLLA, CA—Results of a phase 2 study suggest chidamide can produce durable responses in patients with relapsed/refractory natural killer/T-cell lymphoma (NKTCL).

The overall response rate was 57.2% in these patients, and the complete response (CR) rate was 28.6%.

Seven of 14 evaluable patients were still receiving chidamide and still in response at last follow-up. For one patient, this was 50 weeks from initiating treatment with chidamide.

“The response is quite promising and encouraging,” said study investigator Huiqiang Huang, MD, PhD, of Sun Yat-sen University Cancer Center in Guangzhou, China.

“In terms of safety, the toxicity is mild to moderate.”

Dr Huang presented these results at the 10th Annual T-cell Lymphoma Forum.

This investigator-sponsored trial enrolled patients with relapsed/refractory non-Hodgkin lymphoma, but Dr Huang presented results in NKTCL patients only.

There were 15 NKTCL patients, most of whom were male (n=12). Their median age was 41 (range, 17-65). All 15 had an ECOG status of 0 or 1, 9 had stage I/II disease, and 6 had B symptoms.

Nine patients had Epstein-Barr virus (EBV) DNA levels of at least 1000 copy/mL at baseline, and 5 patients had lactate dehydrogenase levels of at least 245 U/L.

The patients had a median of 2 prior systemic therapies (range, 1-3), and 2 patients had undergone a transplant.

Efficacy

Patients received chidamide at 2 doses—10 mg daily or 30 mg twice a week. Dr Huang said both doses were effective against the lymphoma types studied, but the 30 mg twice-weekly dose appeared to be more effective for patients with NKTCL.

Fourteen NKTCL patients were evaluable for efficacy, and the median follow-up was 17.6 weeks (range, 2.6-50).

The overall response rate was 68.2% (6/14), and the CR rate was 28.6% (4/14). The disease control rate was 71.4%, meaning 10 of 14 patients had a CR, partial response (PR), or stable disease (SD).

Dr Huang noted that response was associated with elevated H3 acetylation level.

The median time to response was 5.25 weeks (range, 1.1-6.6).

As for duration of response, the 4 complete responders were still on treatment and in CR at last follow-up, which was 22.7 weeks, 38.1 weeks, 41.3 weeks, and 50 weeks, respectively, from treatment initiation.

Three of the 4 partial responders were still on treatment and in PR at 14.1 weeks, 26.9 weeks, and 32 weeks, respectively. Two patients with SD were still on treatment and in SD at 15.3 weeks and 15.9 weeks, respectively.

Three patients progressed while on treatment and died. A fourth patient died 2.6 weeks after treatment initiation.

Safety

Dr Huang noted that adverse events (AEs) were similar with the 2 dose groups. However, patients who received 30 mg biweekly had a higher incidence of gastrointestinal AEs.

Overall, the most common AEs were hematologic—anemia, thrombocytopenia, etc.—but dose reductions allowed for quick resolution of these AEs, according to Dr Huang.

AEs included:

• Lymphopenia—10 grade 1/2 and 1 grade 3/4
• Anemia—9 grade 1/2 and 3 grade 3/4
• Thrombocytopenia—7 grade 1/2 and grade 3/4
• Leukopenia—7 grade 1/2 and 6 grade 3/4
• Increased alanine aminotransferase—7 grade 1/2
• Neutropenia—6 grade 1/2 and 7 grade 3/4
• Increased aspartate aminotransferase—5 grade 1/2
• Hypoalbuminemia—4 grade 1/2
• Nausea—4 grade 1/2 and 1 grade 3/4
• Vomiting—3 grade 1/2
• Mucositis—2 grade 1/2
• Fatigue—2 grade 1/2
• Epistaxis—2 grade 1/2
• Abdominal distension—1 grade 1/2
• Loss of appetite—1 grade 1/2
• Diarrhea—1 grade 1/2
• Hyperbilirubinemia—1 grade 1/2
• Fever—1 grade 1/2 and grade 3/4
• Pain—1 grade 1/2
• Cough—1 grade 1/2
• Constipation—1 grade 1/2.

Dr Huang said EBV reactivation was not confirmed in this study. An elevated EBV DNA load was only observed in 2 patients with progressive disease.

Photo by Larry Young

LA JOLLA, CA—A 2-drug combination has demonstrated preferential activity in T-cell lymphomas over B-cell lymphomas, according to researchers.

In a small, phase 1/2 study, treatment with oral 5-azacitidine and romidepsin produced a higher overall response rate (ORR) and prolonged progression-free survival (PFS) in patients with T-cell lymphomas.

“In a very limited sample, we’ve definitely observed exquisite activity of the combination in patients with T-cell lymphoma compared to all other subtypes,” said Lorenzo Falchi, MD, of Columbia University Medical Center in New York, New York.

Dr Falchi presented these results at the 10th Annual T-cell Lymphoma Forum.

The research was funded by the Leukemia and Lymphoma Society, the Lymphoma Research Fund at Columbia University, and Celgene.

The phase 1 portion of this study included patients with previously treated non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma. The phase 2 portion included only patients with T-cell lymphomas, newly diagnosed or previously treated.

Thirty-three patients were enrolled—12 with Hodgkin lymphoma, 8 with B-cell NHL, and 13 with T-cell NHL.

The patients’ median age was 54 (range, 23-79). Fifty-seven percent (n=19) were male. Sixty-one percent of patients were non-Hispanic white (n=20), 24% (n=8) were black, and 12% (n=4) were Asian.

“This was a very heavily pretreated patient population,” Dr Falchi noted. “I’d like to emphasize that the median number of prior treatments is 5 [range, 0-15].”

“Over half of patients had had stem cell transplantation [17 autologous and 5 allogeneic]. And, if you look at the subtypes by histology, all patients, pretty much, at some point, received all the standard chemotherapy or treatment approaches that are typically used for that subtype.”

Treatment

Patients were divided into 7 dosing cohorts. Azacitidine doses ranged from 100 mg to 300 mg on days 1-14 or days 1-21 per cycle.

Romidepsin doses ranged from 10 mg/m² to 14 mg/m². The drug was given on days 8 and 15 every 21 or 28 days, or it was given on days 8, 15, and 22 every 35 days.

There were 2 dose-limiting toxicities (DLTs) in cohort 2—grade 3 thrombocytopenia and grade 3 pleural effusion. In this cohort, 3 patients received azacitidine at 200 mg on days 1-14 plus romidepsin at 10 mg/m² on days 8 and 15 every 21 days.

There were 3 DLTs in cohort 7—2 cases of grade 4 neutropenia and 1 case of grade 3 thrombocytopenia. In this cohort, 5 patients received azacitidine at 300 mg on days 1 to 21 plus romidepsin at 14 mg/m² on days 8, 15, and 22 every 35 days.

Because of the DLTs in cohort 7, cohort 6 was chosen as the maximum tolerated dose. In cohort 6, 3 patients received azacitidine at 300 mg on days 1-14 plus romidepsin at 14 mg/m² on days 8, 15, and 22 every 35 days.

Patients in the expansion cohort received treatment at the maximum tolerated dose. This cohort included 7 patients with T-cell lymphoma.

Safety

Treatment-emergent adverse events occurring in at least 5% of patients included:

• Anemia—3% grade 3
• Anorexia—9% grade 1
• Back pain—6% grade 2
• Constipation—6% grade 1
• Cough—9% grade 1
• Depression—3% grade 1 and 2
• Diarrhea—15% grade 1 and 6% grade 2
• Dyspnea—3% grade 1 and 2
• Fatigue—21% grade 1, 9% grade 2, and 3% grade 3
• Febrile neutropenia—3% grade 3 and 4
• Fever—6% grade 1 and 3% grade 2
• General disorders and administration site conditions—15% grade 1
• Hyperglycemia—3% grade 3
• Hypokalemia—6% grade 1
• Hypotension—3% grade 3
• Insomnia—6% grade 1
• Oral mucositis—9% grade 1 and 3% grade 2
• Nausea—18% grade 1, 27% grade 2, and 3% grade 3
• Neutrophil count decrease—3% grade 3 and 4
• Pain—3% grade 1 and 6% grade 2
• Pain of skin—3% grade 1 and 2
• Platelet count decrease—6% grade 2, 9% grade 3, and 6% grade 4
• Urinary tract infection—3% grade 3
• Vomiting—18% grade 1 and 21% grade 2.

Efficacy

Twenty-eight patients were evaluable for efficacy. The ORR for these patients was 36% (n=10).

The complete response (CR) rate was 22% (n=6), and the partial response (PR) rate was 14% (n=4). Twenty-five percent of patients (n=7) had stable disease, and 39% (n=11) progressed.

Dr Falchi noted that the ORR was “much higher” in patients with T-cell lymphoma than in those with B-cell lymphoma—80% (n=8) and 11% (n=2), respectively.

The CR rates were 50% (n=5) in T-cell lymphoma patients and 5.5% (n=1) in B-cell patients. PR rates were 30% (n=3) and 5.5% (n=1), respectively. Thirty-nine percent (n=7) of B-cell patients had stable disease, but none of the T-cell patients did.

“Patients with non-T-cell lymphoma were much more likely to progress on treatment,” Dr Falchi noted. “Half of them did so [n=9].”

This is in comparison to the 20% of T-cell lymphoma patients who progressed on treatment (n=2).

Disease subtypes for complete responders included transformed follicular lymphoma (n=1), T-lymphoblastic lymphoma (n=1), adult T-cell leukemia/lymphoma (n=1), extranodal NK/T-cell lymphoma (n=1), and angioimmunoblastic T-cell lymphoma (n=2).

Partial responders had follicular lymphoma (n=1), cutaneous peripheral T-cell lymphoma (n=1), cutaneous anaplastic large-cell lymphoma (n=1), and angioimmunoblastic T-cell lymphoma (n=1).

The 2 responders with B-cell lymphoma (1 CR and 1 PR) ultimately progressed and died.

Of the 8 responders with T-cell lymphoma, 3 have an ongoing CR, and 2 of these patients proceeded to transplant.

One T-cell patient who achieved a CR and proceeded to transplant was lost to follow-up. Another died after transplant.

Two T-cell patients who achieved a PR progressed and died. And 1 patient has an ongoing PR.

In total, 75% of patients (n=21) progressed. The median PFS for the entire study cohort was 3.6 months (range, 1.5-5.7).

The median PFS was 2.2 months (range, 1.1-3.2) for patients with B-cell lymphomas and was not reached for the T-cell lymphoma patients.

Eighty-nine percent of B-cell patients progressed (n=16), as did 40% of T-cell patients (n=4).

Dr Falchi and his colleagues are now conducting studies to correlate the pharmacokinetics of azacitidine-romidepsin with genome-wide methylation and correlate TET2, IDH2, and DNMT3A mutation status with clinical response.

Photo by Larry Young

LA JOLLA, CA—A 2-drug combination has demonstrated preferential activity in T-cell lymphomas over B-cell lymphomas, according to researchers.

In a small, phase 1/2 study, treatment with oral 5-azacitidine and romidepsin produced a higher overall response rate (ORR) and prolonged progression-free survival (PFS) in patients with T-cell lymphomas.

“In a very limited sample, we’ve definitely observed exquisite activity of the combination in patients with T-cell lymphoma compared to all other subtypes,” said Lorenzo Falchi, MD, of Columbia University Medical Center in New York, New York.

Dr Falchi presented these results at the 10th Annual T-cell Lymphoma Forum.

The research was funded by the Leukemia and Lymphoma Society, the Lymphoma Research Fund at Columbia University, and Celgene.

The phase 1 portion of this study included patients with previously treated non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma. The phase 2 portion included only patients with T-cell lymphomas, newly diagnosed or previously treated.

Thirty-three patients were enrolled—12 with Hodgkin lymphoma, 8 with B-cell NHL, and 13 with T-cell NHL.

The patients’ median age was 54 (range, 23-79). Fifty-seven percent (n=19) were male. Sixty-one percent of patients were non-Hispanic white (n=20), 24% (n=8) were black, and 12% (n=4) were Asian.

“This was a very heavily pretreated patient population,” Dr Falchi noted. “I’d like to emphasize that the median number of prior treatments is 5 [range, 0-15].”

“Over half of patients had had stem cell transplantation [17 autologous and 5 allogeneic]. And, if you look at the subtypes by histology, all patients, pretty much, at some point, received all the standard chemotherapy or treatment approaches that are typically used for that subtype.”

Treatment

Patients were divided into 7 dosing cohorts. Azacitidine doses ranged from 100 mg to 300 mg on days 1-14 or days 1-21 per cycle.

Romidepsin doses ranged from 10 mg/m² to 14 mg/m². The drug was given on days 8 and 15 every 21 or 28 days, or it was given on days 8, 15, and 22 every 35 days.

There were 2 dose-limiting toxicities (DLTs) in cohort 2—grade 3 thrombocytopenia and grade 3 pleural effusion. In this cohort, 3 patients received azacitidine at 200 mg on days 1-14 plus romidepsin at 10 mg/m² on days 8 and 15 every 21 days.

There were 3 DLTs in cohort 7—2 cases of grade 4 neutropenia and 1 case of grade 3 thrombocytopenia. In this cohort, 5 patients received azacitidine at 300 mg on days 1 to 21 plus romidepsin at 14 mg/m² on days 8, 15, and 22 every 35 days.

Because of the DLTs in cohort 7, cohort 6 was chosen as the maximum tolerated dose. In cohort 6, 3 patients received azacitidine at 300 mg on days 1-14 plus romidepsin at 14 mg/m² on days 8, 15, and 22 every 35 days.

Patients in the expansion cohort received treatment at the maximum tolerated dose. This cohort included 7 patients with T-cell lymphoma.

Safety

Treatment-emergent adverse events occurring in at least 5% of patients included:

• Anemia—3% grade 3
• Anorexia—9% grade 1
• Back pain—6% grade 2
• Constipation—6% grade 1
• Cough—9% grade 1
• Depression—3% grade 1 and 2
• Diarrhea—15% grade 1 and 6% grade 2
• Dyspnea—3% grade 1 and 2
• Fatigue—21% grade 1, 9% grade 2, and 3% grade 3
• Febrile neutropenia—3% grade 3 and 4
• Fever—6% grade 1 and 3% grade 2
• General disorders and administration site conditions—15% grade 1
• Hyperglycemia—3% grade 3
• Hypokalemia—6% grade 1
• Hypotension—3% grade 3
• Insomnia—6% grade 1
• Oral mucositis—9% grade 1 and 3% grade 2
• Nausea—18% grade 1, 27% grade 2, and 3% grade 3
• Neutrophil count decrease—3% grade 3 and 4
• Pain—3% grade 1 and 6% grade 2
• Pain of skin—3% grade 1 and 2
• Platelet count decrease—6% grade 2, 9% grade 3, and 6% grade 4
• Urinary tract infection—3% grade 3
• Vomiting—18% grade 1 and 21% grade 2.

Efficacy

Twenty-eight patients were evaluable for efficacy. The ORR for these patients was 36% (n=10).

The complete response (CR) rate was 22% (n=6), and the partial response (PR) rate was 14% (n=4). Twenty-five percent of patients (n=7) had stable disease, and 39% (n=11) progressed.

Dr Falchi noted that the ORR was “much higher” in patients with T-cell lymphoma than in those with B-cell lymphoma—80% (n=8) and 11% (n=2), respectively.

The CR rates were 50% (n=5) in T-cell lymphoma patients and 5.5% (n=1) in B-cell patients. PR rates were 30% (n=3) and 5.5% (n=1), respectively. Thirty-nine percent (n=7) of B-cell patients had stable disease, but none of the T-cell patients did.

“Patients with non-T-cell lymphoma were much more likely to progress on treatment,” Dr Falchi noted. “Half of them did so [n=9].”

This is in comparison to the 20% of T-cell lymphoma patients who progressed on treatment (n=2).

Disease subtypes for complete responders included transformed follicular lymphoma (n=1), T-lymphoblastic lymphoma (n=1), adult T-cell leukemia/lymphoma (n=1), extranodal NK/T-cell lymphoma (n=1), and angioimmunoblastic T-cell lymphoma (n=2).

Partial responders had follicular lymphoma (n=1), cutaneous peripheral T-cell lymphoma (n=1), cutaneous anaplastic large-cell lymphoma (n=1), and angioimmunoblastic T-cell lymphoma (n=1).

The 2 responders with B-cell lymphoma (1 CR and 1 PR) ultimately progressed and died.

Of the 8 responders with T-cell lymphoma, 3 have an ongoing CR, and 2 of these patients proceeded to transplant.

One T-cell patient who achieved a CR and proceeded to transplant was lost to follow-up. Another died after transplant.

Two T-cell patients who achieved a PR progressed and died. And 1 patient has an ongoing PR.

In total, 75% of patients (n=21) progressed. The median PFS for the entire study cohort was 3.6 months (range, 1.5-5.7).

The median PFS was 2.2 months (range, 1.1-3.2) for patients with B-cell lymphomas and was not reached for the T-cell lymphoma patients.

Eighty-nine percent of B-cell patients progressed (n=16), as did 40% of T-cell patients (n=4).

Dr Falchi and his colleagues are now conducting studies to correlate the pharmacokinetics of azacitidine-romidepsin with genome-wide methylation and correlate TET2, IDH2, and DNMT3A mutation status with clinical response.

Photo by Larry Young

LA JOLLA, CA—A 2-drug combination has demonstrated preferential activity in T-cell lymphomas over B-cell lymphomas, according to researchers.

In a small, phase 1/2 study, treatment with oral 5-azacitidine and romidepsin produced a higher overall response rate (ORR) and prolonged progression-free survival (PFS) in patients with T-cell lymphomas.

“In a very limited sample, we’ve definitely observed exquisite activity of the combination in patients with T-cell lymphoma compared to all other subtypes,” said Lorenzo Falchi, MD, of Columbia University Medical Center in New York, New York.

Dr Falchi presented these results at the 10th Annual T-cell Lymphoma Forum.

The research was funded by the Leukemia and Lymphoma Society, the Lymphoma Research Fund at Columbia University, and Celgene.

The phase 1 portion of this study included patients with previously treated non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma. The phase 2 portion included only patients with T-cell lymphomas, newly diagnosed or previously treated.

Thirty-three patients were enrolled—12 with Hodgkin lymphoma, 8 with B-cell NHL, and 13 with T-cell NHL.

The patients’ median age was 54 (range, 23-79). Fifty-seven percent (n=19) were male. Sixty-one percent of patients were non-Hispanic white (n=20), 24% (n=8) were black, and 12% (n=4) were Asian.

“This was a very heavily pretreated patient population,” Dr Falchi noted. “I’d like to emphasize that the median number of prior treatments is 5 [range, 0-15].”

“Over half of patients had had stem cell transplantation [17 autologous and 5 allogeneic]. And, if you look at the subtypes by histology, all patients, pretty much, at some point, received all the standard chemotherapy or treatment approaches that are typically used for that subtype.”

Treatment

Patients were divided into 7 dosing cohorts. Azacitidine doses ranged from 100 mg to 300 mg on days 1-14 or days 1-21 per cycle.

Romidepsin doses ranged from 10 mg/m² to 14 mg/m². The drug was given on days 8 and 15 every 21 or 28 days, or it was given on days 8, 15, and 22 every 35 days.

There were 2 dose-limiting toxicities (DLTs) in cohort 2—grade 3 thrombocytopenia and grade 3 pleural effusion. In this cohort, 3 patients received azacitidine at 200 mg on days 1-14 plus romidepsin at 10 mg/m² on days 8 and 15 every 21 days.

There were 3 DLTs in cohort 7—2 cases of grade 4 neutropenia and 1 case of grade 3 thrombocytopenia. In this cohort, 5 patients received azacitidine at 300 mg on days 1 to 21 plus romidepsin at 14 mg/m² on days 8, 15, and 22 every 35 days.

Because of the DLTs in cohort 7, cohort 6 was chosen as the maximum tolerated dose. In cohort 6, 3 patients received azacitidine at 300 mg on days 1-14 plus romidepsin at 14 mg/m² on days 8, 15, and 22 every 35 days.

Patients in the expansion cohort received treatment at the maximum tolerated dose. This cohort included 7 patients with T-cell lymphoma.

Safety

Treatment-emergent adverse events occurring in at least 5% of patients included:

• Anemia—3% grade 3
• Anorexia—9% grade 1
• Back pain—6% grade 2
• Constipation—6% grade 1
• Cough—9% grade 1
• Depression—3% grade 1 and 2
• Diarrhea—15% grade 1 and 6% grade 2
• Dyspnea—3% grade 1 and 2
• Fatigue—21% grade 1, 9% grade 2, and 3% grade 3
• Febrile neutropenia—3% grade 3 and 4
• Fever—6% grade 1 and 3% grade 2
• General disorders and administration site conditions—15% grade 1
• Hyperglycemia—3% grade 3
• Hypokalemia—6% grade 1
• Hypotension—3% grade 3
• Insomnia—6% grade 1
• Oral mucositis—9% grade 1 and 3% grade 2
• Nausea—18% grade 1, 27% grade 2, and 3% grade 3
• Neutrophil count decrease—3% grade 3 and 4
• Pain—3% grade 1 and 6% grade 2
• Pain of skin—3% grade 1 and 2
• Platelet count decrease—6% grade 2, 9% grade 3, and 6% grade 4
• Urinary tract infection—3% grade 3
• Vomiting—18% grade 1 and 21% grade 2.

Efficacy

Twenty-eight patients were evaluable for efficacy. The ORR for these patients was 36% (n=10).

The complete response (CR) rate was 22% (n=6), and the partial response (PR) rate was 14% (n=4). Twenty-five percent of patients (n=7) had stable disease, and 39% (n=11) progressed.

Dr Falchi noted that the ORR was “much higher” in patients with T-cell lymphoma than in those with B-cell lymphoma—80% (n=8) and 11% (n=2), respectively.

The CR rates were 50% (n=5) in T-cell lymphoma patients and 5.5% (n=1) in B-cell patients. PR rates were 30% (n=3) and 5.5% (n=1), respectively. Thirty-nine percent (n=7) of B-cell patients had stable disease, but none of the T-cell patients did.

“Patients with non-T-cell lymphoma were much more likely to progress on treatment,” Dr Falchi noted. “Half of them did so [n=9].”

This is in comparison to the 20% of T-cell lymphoma patients who progressed on treatment (n=2).

Disease subtypes for complete responders included transformed follicular lymphoma (n=1), T-lymphoblastic lymphoma (n=1), adult T-cell leukemia/lymphoma (n=1), extranodal NK/T-cell lymphoma (n=1), and angioimmunoblastic T-cell lymphoma (n=2).

Partial responders had follicular lymphoma (n=1), cutaneous peripheral T-cell lymphoma (n=1), cutaneous anaplastic large-cell lymphoma (n=1), and angioimmunoblastic T-cell lymphoma (n=1).

The 2 responders with B-cell lymphoma (1 CR and 1 PR) ultimately progressed and died.

Of the 8 responders with T-cell lymphoma, 3 have an ongoing CR, and 2 of these patients proceeded to transplant.

One T-cell patient who achieved a CR and proceeded to transplant was lost to follow-up. Another died after transplant.

Two T-cell patients who achieved a PR progressed and died. And 1 patient has an ongoing PR.

In total, 75% of patients (n=21) progressed. The median PFS for the entire study cohort was 3.6 months (range, 1.5-5.7).

The median PFS was 2.2 months (range, 1.1-3.2) for patients with B-cell lymphomas and was not reached for the T-cell lymphoma patients.

Eighty-nine percent of B-cell patients progressed (n=16), as did 40% of T-cell patients (n=4).

Dr Falchi and his colleagues are now conducting studies to correlate the pharmacokinetics of azacitidine-romidepsin with genome-wide methylation and correlate TET2, IDH2, and DNMT3A mutation status with clinical response.

Photo by Larry Young

LA JOLLA, CA—Phase 1 results suggest duvelisib combination therapies can be active and well-tolerated in patients with relapsed/refractory T-cell lymphomas.

Researchers said duvelisib had an acceptable safety profile when given in combination with romidepsin or bortezomib to patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL).

Duvelisib plus romidepsin produced a 60% overall response rate (ORR) in these patients, and duvelisib plus bortezomib produced a 35% ORR.

Response rates were higher in PTCL patients than CTCL patients.

Neha Mehta-Shah, MD, of Washington University in St. Louis, Missouri, and her colleagues presented these results in a poster at the 10th Annual T-cell Lymphoma Forum.

The research was supported by the Leukemia & Lymphoma Society, Infinity Pharmaceuticals, and Verastem Inc.

This phase 1 trial consists of parallel arms evaluating duvelisib in combination with romidepsin (arm A) or bortezomib (arm B). The trial enrolled patients with PTCL or CTCL that had progressed after at least 1 prior therapy.

All patients received duvelisib at 25 mg, 50 mg, or 75 mg twice daily for 28-day cycles.

Patients in arm A received romidepsin at 10 mg/m² on days 1, 8, and 15 of each cycle.

Patients in arm B received bortezomib at 1 mg/m² on days 1, 4, 8, and 11 of each cycle.

Romidepsin combination

Sixteen patients received duvelisib plus romidepsin, and 15 of them were evaluable for efficacy. Eleven patients had PTCL, and 4 had CTCL.

The ORR was 60% (9/16), and the complete response (CR) rate was 27% (n=4). The median time to response was 51 days (range, 49-54).

The ORR was 64% in the PTCL patients and 50% in the CTCL patients. All 4 CRs occurred in PTCL patients, 2 in patients with PTCL not otherwise specified (NOS) and 2 in patients with angioimmunoblastic T-cell lymphoma (AITL).

There were 5 responses among patients who received the 75 mg dose of duvelisib (n=8) and 2 responses each in the 50 mg dose group (n=3) and 25 mg dose group (n=4).

There were no dose-limiting toxicities, so the 75 mg dose of duvelisib was considered the maximum tolerated dose.

All 16 patients were evaluable for safety. There were 2 serious adverse events (AEs) considered possibly related to treatment—grade 3 fatigue and grade 2 aspartate aminotransferase (AST) increase.

There were 2 deaths considered unrelated to treatment—diffuse alveolar hemorrhage after allogeneic transplant and sepsis in the setting of disease progression.

Treatment-related AEs (occurring in at least 2 patients) were fatigue (56%), nausea (50%), altered taste (50%), diarrhea (38%), neutropenia (38%), rash (31%), thrombocytopenia (25%), dysphagia (25%), and anorexia (25%).

Grade 3/4 treatment-related AEs included neutropenia (38%) and thrombocytopenia (6%).

One patient discontinued duvelisib-romidepsin due to toxicity, and 7 discontinued due to progressive disease.

Three patients proceeded to bone marrow transplant/donor lymphocyte infusion, and 4 patients are still receiving study treatment.

Bortezomib combination

There were 17 patients who received duvelisib plus bortezomib—10 with PTCL and 7 with CTCL.

The ORR was 35% (6/17), and the CR rate was 18% (n=3). The median time to response was 52 days (range, 47-57).

The ORR was 50% in PTCL patients and 14% among CTCL patients.

All 3 CRs occurred in the PTCL patients—1 in a patient with AITL, 1 in a patient with PTCL-NOS, and 1 in a patient who had intestinal T-cell lymphoma with B-cell lymphoproliferative disorder.

There were 3 responses among patients who received the 25 mg dose of duvelisib (n=8), 2 responses in the 50 mg dose group (n=3), and 1 response in the 75 mg dose group (n=6).

There was 1 dose-limiting toxicity—pneumonia—in a patient treated at the 25 mg dose.

The 25 mg dose was deemed optimal due to grade 3 alanine transaminase (ALT)/AST elevations observed after cycle 1 with the 50 mg dose (n=3) and the 75 mg dose (n=2).

There were 6 serious AEs considered possibly related to treatment:

• Grade 3 pneumonia (n=2)
• Grade 3 infectious colitis (n=1)
• Grade 3 colitis (n=1)
• Grade 4 ALT/AST elevation (n=1)
• Grade 5 Stevens-Johnson syndrome (n=1).

The fatal case of Stevens-Johnson syndrome was considered possibly related to bortezomib, duvelisib, and trimethoprim-sulfamethoxazole, a medication that was started at the beginning of the study.

Treatment-related AEs (occurring in at least 2 patients) included diarrhea/colitis (71%), ALT/AST increase (41%), rash (24%), neutropenia (24%), nausea/vomiting (24%), chills (24%), fatigue (24%), and alkaline phosphatase increase (12%).

Grade 3/4 AEs included ALT/AST increase (35%), rash (12%), neutropenia (12%), diarrhea/colitis (6%), and alkaline phosphatase increase (6%).

Seven patients discontinued duvelisib-bortezomib due to toxicity, and 8 discontinued due to disease progression. Two patients are still on study treatment.

Photo by Larry Young

LA JOLLA, CA—Phase 1 results suggest duvelisib combination therapies can be active and well-tolerated in patients with relapsed/refractory T-cell lymphomas.

Researchers said duvelisib had an acceptable safety profile when given in combination with romidepsin or bortezomib to patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL).

Duvelisib plus romidepsin produced a 60% overall response rate (ORR) in these patients, and duvelisib plus bortezomib produced a 35% ORR.

Response rates were higher in PTCL patients than CTCL patients.

Neha Mehta-Shah, MD, of Washington University in St. Louis, Missouri, and her colleagues presented these results in a poster at the 10th Annual T-cell Lymphoma Forum.

The research was supported by the Leukemia & Lymphoma Society, Infinity Pharmaceuticals, and Verastem Inc.

This phase 1 trial consists of parallel arms evaluating duvelisib in combination with romidepsin (arm A) or bortezomib (arm B). The trial enrolled patients with PTCL or CTCL that had progressed after at least 1 prior therapy.

All patients received duvelisib at 25 mg, 50 mg, or 75 mg twice daily for 28-day cycles.

Patients in arm A received romidepsin at 10 mg/m² on days 1, 8, and 15 of each cycle.

Patients in arm B received bortezomib at 1 mg/m² on days 1, 4, 8, and 11 of each cycle.

Romidepsin combination

Sixteen patients received duvelisib plus romidepsin, and 15 of them were evaluable for efficacy. Eleven patients had PTCL, and 4 had CTCL.

The ORR was 60% (9/16), and the complete response (CR) rate was 27% (n=4). The median time to response was 51 days (range, 49-54).

The ORR was 64% in the PTCL patients and 50% in the CTCL patients. All 4 CRs occurred in PTCL patients, 2 in patients with PTCL not otherwise specified (NOS) and 2 in patients with angioimmunoblastic T-cell lymphoma (AITL).

There were 5 responses among patients who received the 75 mg dose of duvelisib (n=8) and 2 responses each in the 50 mg dose group (n=3) and 25 mg dose group (n=4).

There were no dose-limiting toxicities, so the 75 mg dose of duvelisib was considered the maximum tolerated dose.

All 16 patients were evaluable for safety. There were 2 serious adverse events (AEs) considered possibly related to treatment—grade 3 fatigue and grade 2 aspartate aminotransferase (AST) increase.

There were 2 deaths considered unrelated to treatment—diffuse alveolar hemorrhage after allogeneic transplant and sepsis in the setting of disease progression.

Treatment-related AEs (occurring in at least 2 patients) were fatigue (56%), nausea (50%), altered taste (50%), diarrhea (38%), neutropenia (38%), rash (31%), thrombocytopenia (25%), dysphagia (25%), and anorexia (25%).

Grade 3/4 treatment-related AEs included neutropenia (38%) and thrombocytopenia (6%).

One patient discontinued duvelisib-romidepsin due to toxicity, and 7 discontinued due to progressive disease.

Three patients proceeded to bone marrow transplant/donor lymphocyte infusion, and 4 patients are still receiving study treatment.

Bortezomib combination

There were 17 patients who received duvelisib plus bortezomib—10 with PTCL and 7 with CTCL.

The ORR was 35% (6/17), and the CR rate was 18% (n=3). The median time to response was 52 days (range, 47-57).

The ORR was 50% in PTCL patients and 14% among CTCL patients.

All 3 CRs occurred in the PTCL patients—1 in a patient with AITL, 1 in a patient with PTCL-NOS, and 1 in a patient who had intestinal T-cell lymphoma with B-cell lymphoproliferative disorder.

There were 3 responses among patients who received the 25 mg dose of duvelisib (n=8), 2 responses in the 50 mg dose group (n=3), and 1 response in the 75 mg dose group (n=6).

There was 1 dose-limiting toxicity—pneumonia—in a patient treated at the 25 mg dose.

The 25 mg dose was deemed optimal due to grade 3 alanine transaminase (ALT)/AST elevations observed after cycle 1 with the 50 mg dose (n=3) and the 75 mg dose (n=2).

There were 6 serious AEs considered possibly related to treatment:

• Grade 3 pneumonia (n=2)
• Grade 3 infectious colitis (n=1)
• Grade 3 colitis (n=1)
• Grade 4 ALT/AST elevation (n=1)
• Grade 5 Stevens-Johnson syndrome (n=1).

The fatal case of Stevens-Johnson syndrome was considered possibly related to bortezomib, duvelisib, and trimethoprim-sulfamethoxazole, a medication that was started at the beginning of the study.

Treatment-related AEs (occurring in at least 2 patients) included diarrhea/colitis (71%), ALT/AST increase (41%), rash (24%), neutropenia (24%), nausea/vomiting (24%), chills (24%), fatigue (24%), and alkaline phosphatase increase (12%).

Grade 3/4 AEs included ALT/AST increase (35%), rash (12%), neutropenia (12%), diarrhea/colitis (6%), and alkaline phosphatase increase (6%).

Seven patients discontinued duvelisib-bortezomib due to toxicity, and 8 discontinued due to disease progression. Two patients are still on study treatment.

Photo by Larry Young

LA JOLLA, CA—Phase 1 results suggest duvelisib combination therapies can be active and well-tolerated in patients with relapsed/refractory T-cell lymphomas.

Researchers said duvelisib had an acceptable safety profile when given in combination with romidepsin or bortezomib to patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL).

Duvelisib plus romidepsin produced a 60% overall response rate (ORR) in these patients, and duvelisib plus bortezomib produced a 35% ORR.

Response rates were higher in PTCL patients than CTCL patients.

Neha Mehta-Shah, MD, of Washington University in St. Louis, Missouri, and her colleagues presented these results in a poster at the 10th Annual T-cell Lymphoma Forum.

The research was supported by the Leukemia & Lymphoma Society, Infinity Pharmaceuticals, and Verastem Inc.

This phase 1 trial consists of parallel arms evaluating duvelisib in combination with romidepsin (arm A) or bortezomib (arm B). The trial enrolled patients with PTCL or CTCL that had progressed after at least 1 prior therapy.

All patients received duvelisib at 25 mg, 50 mg, or 75 mg twice daily for 28-day cycles.

Patients in arm A received romidepsin at 10 mg/m² on days 1, 8, and 15 of each cycle.

Patients in arm B received bortezomib at 1 mg/m² on days 1, 4, 8, and 11 of each cycle.

Romidepsin combination

Sixteen patients received duvelisib plus romidepsin, and 15 of them were evaluable for efficacy. Eleven patients had PTCL, and 4 had CTCL.

The ORR was 60% (9/16), and the complete response (CR) rate was 27% (n=4). The median time to response was 51 days (range, 49-54).

The ORR was 64% in the PTCL patients and 50% in the CTCL patients. All 4 CRs occurred in PTCL patients, 2 in patients with PTCL not otherwise specified (NOS) and 2 in patients with angioimmunoblastic T-cell lymphoma (AITL).

There were 5 responses among patients who received the 75 mg dose of duvelisib (n=8) and 2 responses each in the 50 mg dose group (n=3) and 25 mg dose group (n=4).

There were no dose-limiting toxicities, so the 75 mg dose of duvelisib was considered the maximum tolerated dose.

All 16 patients were evaluable for safety. There were 2 serious adverse events (AEs) considered possibly related to treatment—grade 3 fatigue and grade 2 aspartate aminotransferase (AST) increase.

There were 2 deaths considered unrelated to treatment—diffuse alveolar hemorrhage after allogeneic transplant and sepsis in the setting of disease progression.

Treatment-related AEs (occurring in at least 2 patients) were fatigue (56%), nausea (50%), altered taste (50%), diarrhea (38%), neutropenia (38%), rash (31%), thrombocytopenia (25%), dysphagia (25%), and anorexia (25%).

Grade 3/4 treatment-related AEs included neutropenia (38%) and thrombocytopenia (6%).

One patient discontinued duvelisib-romidepsin due to toxicity, and 7 discontinued due to progressive disease.

Three patients proceeded to bone marrow transplant/donor lymphocyte infusion, and 4 patients are still receiving study treatment.

Bortezomib combination

There were 17 patients who received duvelisib plus bortezomib—10 with PTCL and 7 with CTCL.

The ORR was 35% (6/17), and the CR rate was 18% (n=3). The median time to response was 52 days (range, 47-57).

The ORR was 50% in PTCL patients and 14% among CTCL patients.

All 3 CRs occurred in the PTCL patients—1 in a patient with AITL, 1 in a patient with PTCL-NOS, and 1 in a patient who had intestinal T-cell lymphoma with B-cell lymphoproliferative disorder.

There were 3 responses among patients who received the 25 mg dose of duvelisib (n=8), 2 responses in the 50 mg dose group (n=3), and 1 response in the 75 mg dose group (n=6).

There was 1 dose-limiting toxicity—pneumonia—in a patient treated at the 25 mg dose.

The 25 mg dose was deemed optimal due to grade 3 alanine transaminase (ALT)/AST elevations observed after cycle 1 with the 50 mg dose (n=3) and the 75 mg dose (n=2).

There were 6 serious AEs considered possibly related to treatment:

• Grade 3 pneumonia (n=2)
• Grade 3 infectious colitis (n=1)
• Grade 3 colitis (n=1)
• Grade 4 ALT/AST elevation (n=1)
• Grade 5 Stevens-Johnson syndrome (n=1).

The fatal case of Stevens-Johnson syndrome was considered possibly related to bortezomib, duvelisib, and trimethoprim-sulfamethoxazole, a medication that was started at the beginning of the study.

Treatment-related AEs (occurring in at least 2 patients) included diarrhea/colitis (71%), ALT/AST increase (41%), rash (24%), neutropenia (24%), nausea/vomiting (24%), chills (24%), fatigue (24%), and alkaline phosphatase increase (12%).

Grade 3/4 AEs included ALT/AST increase (35%), rash (12%), neutropenia (12%), diarrhea/colitis (6%), and alkaline phosphatase increase (6%).

Seven patients discontinued duvelisib-bortezomib due to toxicity, and 8 discontinued due to disease progression. Two patients are still on study treatment.

The addition of pomalidomide to bortezomib and low-dose dexamethasone showed a statistically significant improvement in progression-free survival for patients with relapsed/refractory multiple myeloma, compared with just the two agents, according to Celgene.

Celgene, which markets pomalidomide, announced the results from the phase 3 OPTIMISMM trial (NCT01734928) on Feb. 6. The company expects the results to be presented at future medical meetings, they said.

OPTIMISMM is the first phase 3 trial to examine a triple-drug combination for multiple myeloma patients who have all received prior lenalidomide, Celgene noted.

The pomalidomide/bortezomib/low-dose dexamethasone combination is not currently approved, but pomalidomide plus dexamethasone is approved for multiple myeloma patients who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor, and have shown disease progression within 60 days of last therapy.

mschneider@frontlinemedcom.com

The addition of pomalidomide to bortezomib and low-dose dexamethasone showed a statistically significant improvement in progression-free survival for patients with relapsed/refractory multiple myeloma, compared with just the two agents, according to Celgene.

Celgene, which markets pomalidomide, announced the results from the phase 3 OPTIMISMM trial (NCT01734928) on Feb. 6. The company expects the results to be presented at future medical meetings, they said.

OPTIMISMM is the first phase 3 trial to examine a triple-drug combination for multiple myeloma patients who have all received prior lenalidomide, Celgene noted.

The pomalidomide/bortezomib/low-dose dexamethasone combination is not currently approved, but pomalidomide plus dexamethasone is approved for multiple myeloma patients who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor, and have shown disease progression within 60 days of last therapy.

mschneider@frontlinemedcom.com

The addition of pomalidomide to bortezomib and low-dose dexamethasone showed a statistically significant improvement in progression-free survival for patients with relapsed/refractory multiple myeloma, compared with just the two agents, according to Celgene.

Celgene, which markets pomalidomide, announced the results from the phase 3 OPTIMISMM trial (NCT01734928) on Feb. 6. The company expects the results to be presented at future medical meetings, they said.

OPTIMISMM is the first phase 3 trial to examine a triple-drug combination for multiple myeloma patients who have all received prior lenalidomide, Celgene noted.

The pomalidomide/bortezomib/low-dose dexamethasone combination is not currently approved, but pomalidomide plus dexamethasone is approved for multiple myeloma patients who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor, and have shown disease progression within 60 days of last therapy.

mschneider@frontlinemedcom.com

SAN FRANCISCO – The CD19-directed 4-1BB chimeric antigen receptor (CAR) T-cell product JCAR017 demonstrated increased CAR T-cell expansion and persistence, and higher durability of response at higher dose levels – with manageable toxicities – in a pivotal phase 1 trial of relapsed/refractory B-cell non-Hodgkin lymphoma.

However, preliminary modeling data suggest that a therapeutic window exists for the CAR T-cell expansion, which means that development of strategies for pushing patients into that window could enhance efficacy and limit toxicity associated with JCAR017, Tanya Siddiqi, MD, of City of Hope Comprehensive Cancer Center, Duarte, Calif., reported at the ASCO-SITC Clinical Immuno-Oncology Symposium.

TRANSCEND NHL 001 is a multicenter, seamless design, pivotal trial, which started as a phase 1 first-in-human study of JCAR017, a defined composition CAR T-cell product also known as lisocabtagene maraleucel and administered at precise doses of CD4+ and CD8+ CAR T cells. Dose-finding and dose-expansion cohorts have been investigated, and currently the pivotal diffuse large B-cell lymphoma (DLBCL) cohort is enrolling, Dr. Saddiqi said, noting that dose level 2 (1 x 10⁸ cells given as a single dose) was selected for that cohort.

The current findings are based on the TRANSCEND core population – a set of patients selected from the dose-finding and dose-expansion cohorts. This population includes patients with DLBCL not otherwise specified, transformed follicular lymphoma, or high-grade double- or triple-hit lymphomas, she said, explaining that she and her colleagues looked at prelymphodepletion baseline patient characteristics and biomarkers to assess how they related to outcomes and toxicities. This precise dosing of JCAR017 reduces variability, enabling the identification of potential patient factors associated with clinical outcomes, she said.

Response rates among 27 patients who received dose level 2 were high, with an 81% overall response rate and a 63% complete response rate.

“Patients with complete remission seemed to have more of a durable response,” she said. “In the core population at dose level 2, 50% with 6 months of follow-up seemed to remain in complete response, so there’s a dose-response effect in these patients.”

It doesn’t appear that the dose affects development of cytokine release syndrome (CRS) or neurotoxicity (NT), as the rates of these (30% and 20%, respectively) did not differ by dose level or schedule, but certain baseline features, such as a lactate dehydrogenase (LDH) level above 500 U/L and tumor burden measured as the sum of the product of diameters of 50 cm or greater, do appear to affect the development of these toxicities.

For example, 10 of 13 (77%) of patients with both of those baseline characteristics developed CRS, and 7 of 13 (54%) developed NT; for those without these characteristics, the odds of developing CRS and NT were significantly lower, she said.

Of note, higher C_max, or peak expansion of CAR T cells in vivo, was seen at dose level 2, and exposure (area under the curve) was also higher, as was expected at that dose level, Dr. Siddiqi said.

“It also appears that there is a trend of patients with higher tumor burden to have higher expansion of their CAR T cells in vivo,” she said, noting that some of those patients were “superexpanders” with very high expansion of CAR T cells. “Similarly there were certain cytokines at the prelymphodepletion time point that seem to be higher … in patients who also go on to have higher expansion of their CAR T cells.”

These included interleukin-7, IL-15, MIP (macrophage inflammatory protein)–1alpha, and tumor necrosis factor (TNF)–alpha.

“Patients with certain higher inflammatory cytokines and biomarkers of inflammation also were noted to have higher events of CRS and neurotoxicity, so not just higher tumor burden, but also higher inflammatory state at baseline seems to affect patients in terms of getting any grade CRS or any grade neurotoxicity,” she said.

Those associated with CRS included ferritin, C-reactive protein (CRP), IL-10, IL-15, IL-16, TNF-alpha, and MIP-1beta levels, and those associated with NT included ferritin, CRP, d-dimer, IL-6, IL-15, TNF-alpha, and MIP-1alpha levels.

“Interestingly, there’s an inverse relationship between the expression of some of these biomarkers and inflammatory markers and the durability of response at 3 months,” she said.

Patients with higher tumor burden, LDH, and other markers either had no response at 3 months, or they had a very rapid response at the 1-month mark and then lost their response by 3 months, she noted.

“One of the theories could be that these patients with higher tumor burden, higher inflammatory state – they have such a high peak expansion rapidly after receiving their CAR T cells that potentially those CAR T cells may be getting exhausted or dying off very quickly, and therefore patients can lose their response,” she said.

When these data are considered together and modeled, there seems to be a therapeutic window where patients who have optimal expansion of CAR T cells in vivo may have lesser toxicity, higher overall response rates, and better durability of response, she said.

That is, on one end of the spectrum, there are patients with lower CAR T-cell expansion who have lower toxicities, but who also have lower overall response rates and lower durability of response, and on the other end, there are patients with superhigh expansion of CAR T cells, who have higher response rates, but also higher rates of toxicity, and who lose their response quickly.

“So if we can identify patients who would be in this window of optimal target expansion of CAR T cells, and if we could find strategies or mechanisms to move patients who are on either end of that spectrum into this window, we may be able to get patients with better efficacy and lower toxicities, and there could be combination strategies that could help get us there,” she said.

TRANSCEND NHL 001 is sponsored by Juno Therapeutics. Dr. Siddiqi reported serving as a consultant or adviser for Juno Therapeutics, and as a member of the speakers bureau for Pharmacyclics/Janssen and Seattle Genetics. Research funding was provided to her institution by Juno Therapeutics and several other companies.

sworcester@frontlinemedcom.com

SOURCE: Siddiqi T et al. ASCO-SITC, abstract 122.

SAN FRANCISCO – The CD19-directed 4-1BB chimeric antigen receptor (CAR) T-cell product JCAR017 demonstrated increased CAR T-cell expansion and persistence, and higher durability of response at higher dose levels – with manageable toxicities – in a pivotal phase 1 trial of relapsed/refractory B-cell non-Hodgkin lymphoma.

However, preliminary modeling data suggest that a therapeutic window exists for the CAR T-cell expansion, which means that development of strategies for pushing patients into that window could enhance efficacy and limit toxicity associated with JCAR017, Tanya Siddiqi, MD, of City of Hope Comprehensive Cancer Center, Duarte, Calif., reported at the ASCO-SITC Clinical Immuno-Oncology Symposium.

TRANSCEND NHL 001 is a multicenter, seamless design, pivotal trial, which started as a phase 1 first-in-human study of JCAR017, a defined composition CAR T-cell product also known as lisocabtagene maraleucel and administered at precise doses of CD4+ and CD8+ CAR T cells. Dose-finding and dose-expansion cohorts have been investigated, and currently the pivotal diffuse large B-cell lymphoma (DLBCL) cohort is enrolling, Dr. Saddiqi said, noting that dose level 2 (1 x 10⁸ cells given as a single dose) was selected for that cohort.

The current findings are based on the TRANSCEND core population – a set of patients selected from the dose-finding and dose-expansion cohorts. This population includes patients with DLBCL not otherwise specified, transformed follicular lymphoma, or high-grade double- or triple-hit lymphomas, she said, explaining that she and her colleagues looked at prelymphodepletion baseline patient characteristics and biomarkers to assess how they related to outcomes and toxicities. This precise dosing of JCAR017 reduces variability, enabling the identification of potential patient factors associated with clinical outcomes, she said.

Response rates among 27 patients who received dose level 2 were high, with an 81% overall response rate and a 63% complete response rate.

“Patients with complete remission seemed to have more of a durable response,” she said. “In the core population at dose level 2, 50% with 6 months of follow-up seemed to remain in complete response, so there’s a dose-response effect in these patients.”

It doesn’t appear that the dose affects development of cytokine release syndrome (CRS) or neurotoxicity (NT), as the rates of these (30% and 20%, respectively) did not differ by dose level or schedule, but certain baseline features, such as a lactate dehydrogenase (LDH) level above 500 U/L and tumor burden measured as the sum of the product of diameters of 50 cm or greater, do appear to affect the development of these toxicities.

For example, 10 of 13 (77%) of patients with both of those baseline characteristics developed CRS, and 7 of 13 (54%) developed NT; for those without these characteristics, the odds of developing CRS and NT were significantly lower, she said.

Of note, higher C_max, or peak expansion of CAR T cells in vivo, was seen at dose level 2, and exposure (area under the curve) was also higher, as was expected at that dose level, Dr. Siddiqi said.

“It also appears that there is a trend of patients with higher tumor burden to have higher expansion of their CAR T cells in vivo,” she said, noting that some of those patients were “superexpanders” with very high expansion of CAR T cells. “Similarly there were certain cytokines at the prelymphodepletion time point that seem to be higher … in patients who also go on to have higher expansion of their CAR T cells.”

These included interleukin-7, IL-15, MIP (macrophage inflammatory protein)–1alpha, and tumor necrosis factor (TNF)–alpha.

“Patients with certain higher inflammatory cytokines and biomarkers of inflammation also were noted to have higher events of CRS and neurotoxicity, so not just higher tumor burden, but also higher inflammatory state at baseline seems to affect patients in terms of getting any grade CRS or any grade neurotoxicity,” she said.

Those associated with CRS included ferritin, C-reactive protein (CRP), IL-10, IL-15, IL-16, TNF-alpha, and MIP-1beta levels, and those associated with NT included ferritin, CRP, d-dimer, IL-6, IL-15, TNF-alpha, and MIP-1alpha levels.

“Interestingly, there’s an inverse relationship between the expression of some of these biomarkers and inflammatory markers and the durability of response at 3 months,” she said.

Patients with higher tumor burden, LDH, and other markers either had no response at 3 months, or they had a very rapid response at the 1-month mark and then lost their response by 3 months, she noted.

“One of the theories could be that these patients with higher tumor burden, higher inflammatory state – they have such a high peak expansion rapidly after receiving their CAR T cells that potentially those CAR T cells may be getting exhausted or dying off very quickly, and therefore patients can lose their response,” she said.

When these data are considered together and modeled, there seems to be a therapeutic window where patients who have optimal expansion of CAR T cells in vivo may have lesser toxicity, higher overall response rates, and better durability of response, she said.

That is, on one end of the spectrum, there are patients with lower CAR T-cell expansion who have lower toxicities, but who also have lower overall response rates and lower durability of response, and on the other end, there are patients with superhigh expansion of CAR T cells, who have higher response rates, but also higher rates of toxicity, and who lose their response quickly.

“So if we can identify patients who would be in this window of optimal target expansion of CAR T cells, and if we could find strategies or mechanisms to move patients who are on either end of that spectrum into this window, we may be able to get patients with better efficacy and lower toxicities, and there could be combination strategies that could help get us there,” she said.

TRANSCEND NHL 001 is sponsored by Juno Therapeutics. Dr. Siddiqi reported serving as a consultant or adviser for Juno Therapeutics, and as a member of the speakers bureau for Pharmacyclics/Janssen and Seattle Genetics. Research funding was provided to her institution by Juno Therapeutics and several other companies.

sworcester@frontlinemedcom.com

SOURCE: Siddiqi T et al. ASCO-SITC, abstract 122.

SAN FRANCISCO – The CD19-directed 4-1BB chimeric antigen receptor (CAR) T-cell product JCAR017 demonstrated increased CAR T-cell expansion and persistence, and higher durability of response at higher dose levels – with manageable toxicities – in a pivotal phase 1 trial of relapsed/refractory B-cell non-Hodgkin lymphoma.

However, preliminary modeling data suggest that a therapeutic window exists for the CAR T-cell expansion, which means that development of strategies for pushing patients into that window could enhance efficacy and limit toxicity associated with JCAR017, Tanya Siddiqi, MD, of City of Hope Comprehensive Cancer Center, Duarte, Calif., reported at the ASCO-SITC Clinical Immuno-Oncology Symposium.

TRANSCEND NHL 001 is a multicenter, seamless design, pivotal trial, which started as a phase 1 first-in-human study of JCAR017, a defined composition CAR T-cell product also known as lisocabtagene maraleucel and administered at precise doses of CD4+ and CD8+ CAR T cells. Dose-finding and dose-expansion cohorts have been investigated, and currently the pivotal diffuse large B-cell lymphoma (DLBCL) cohort is enrolling, Dr. Saddiqi said, noting that dose level 2 (1 x 10⁸ cells given as a single dose) was selected for that cohort.

The current findings are based on the TRANSCEND core population – a set of patients selected from the dose-finding and dose-expansion cohorts. This population includes patients with DLBCL not otherwise specified, transformed follicular lymphoma, or high-grade double- or triple-hit lymphomas, she said, explaining that she and her colleagues looked at prelymphodepletion baseline patient characteristics and biomarkers to assess how they related to outcomes and toxicities. This precise dosing of JCAR017 reduces variability, enabling the identification of potential patient factors associated with clinical outcomes, she said.

Response rates among 27 patients who received dose level 2 were high, with an 81% overall response rate and a 63% complete response rate.

“Patients with complete remission seemed to have more of a durable response,” she said. “In the core population at dose level 2, 50% with 6 months of follow-up seemed to remain in complete response, so there’s a dose-response effect in these patients.”

It doesn’t appear that the dose affects development of cytokine release syndrome (CRS) or neurotoxicity (NT), as the rates of these (30% and 20%, respectively) did not differ by dose level or schedule, but certain baseline features, such as a lactate dehydrogenase (LDH) level above 500 U/L and tumor burden measured as the sum of the product of diameters of 50 cm or greater, do appear to affect the development of these toxicities.

For example, 10 of 13 (77%) of patients with both of those baseline characteristics developed CRS, and 7 of 13 (54%) developed NT; for those without these characteristics, the odds of developing CRS and NT were significantly lower, she said.

Of note, higher C_max, or peak expansion of CAR T cells in vivo, was seen at dose level 2, and exposure (area under the curve) was also higher, as was expected at that dose level, Dr. Siddiqi said.

“It also appears that there is a trend of patients with higher tumor burden to have higher expansion of their CAR T cells in vivo,” she said, noting that some of those patients were “superexpanders” with very high expansion of CAR T cells. “Similarly there were certain cytokines at the prelymphodepletion time point that seem to be higher … in patients who also go on to have higher expansion of their CAR T cells.”

These included interleukin-7, IL-15, MIP (macrophage inflammatory protein)–1alpha, and tumor necrosis factor (TNF)–alpha.

“Patients with certain higher inflammatory cytokines and biomarkers of inflammation also were noted to have higher events of CRS and neurotoxicity, so not just higher tumor burden, but also higher inflammatory state at baseline seems to affect patients in terms of getting any grade CRS or any grade neurotoxicity,” she said.

Those associated with CRS included ferritin, C-reactive protein (CRP), IL-10, IL-15, IL-16, TNF-alpha, and MIP-1beta levels, and those associated with NT included ferritin, CRP, d-dimer, IL-6, IL-15, TNF-alpha, and MIP-1alpha levels.

“Interestingly, there’s an inverse relationship between the expression of some of these biomarkers and inflammatory markers and the durability of response at 3 months,” she said.

Patients with higher tumor burden, LDH, and other markers either had no response at 3 months, or they had a very rapid response at the 1-month mark and then lost their response by 3 months, she noted.

“One of the theories could be that these patients with higher tumor burden, higher inflammatory state – they have such a high peak expansion rapidly after receiving their CAR T cells that potentially those CAR T cells may be getting exhausted or dying off very quickly, and therefore patients can lose their response,” she said.

When these data are considered together and modeled, there seems to be a therapeutic window where patients who have optimal expansion of CAR T cells in vivo may have lesser toxicity, higher overall response rates, and better durability of response, she said.

That is, on one end of the spectrum, there are patients with lower CAR T-cell expansion who have lower toxicities, but who also have lower overall response rates and lower durability of response, and on the other end, there are patients with superhigh expansion of CAR T cells, who have higher response rates, but also higher rates of toxicity, and who lose their response quickly.

“So if we can identify patients who would be in this window of optimal target expansion of CAR T cells, and if we could find strategies or mechanisms to move patients who are on either end of that spectrum into this window, we may be able to get patients with better efficacy and lower toxicities, and there could be combination strategies that could help get us there,” she said.

TRANSCEND NHL 001 is sponsored by Juno Therapeutics. Dr. Siddiqi reported serving as a consultant or adviser for Juno Therapeutics, and as a member of the speakers bureau for Pharmacyclics/Janssen and Seattle Genetics. Research funding was provided to her institution by Juno Therapeutics and several other companies.

sworcester@frontlinemedcom.com

SOURCE: Siddiqi T et al. ASCO-SITC, abstract 122.

Red and white blood cells

The US Food and Drug Administration (FDA) says it is evaluating reports of venous thromboembolism (VTE) in patients treated with the CELLEX Photopheresis System by Therakos, Inc.

This extracorporeal photopheresis (ECP) device system is FDA-approved for use in patients with cutaneous T-cell lymphoma (CTCL).

The system is used to perform ultraviolet-A irradiation of a patient’s own leukocyte-enriched blood that is then used as palliative treatment for skin manifestations of CTCL that are unresponsive to other forms of treatment.

The CELLEX Photopheresis System is also used to treat graft-vs-host disease (GVHD) that is resistant to standard immunosuppressive therapy and acute cardiac allograft rejection that is resistant to standard immunosuppressive therapy.

The CELLEX Photopheresis System uses methoxsalen as a photosensitizing agent and heparin as an anticoagulant.

Since 2012, the FDA has received 7 reports of pulmonary embolism (PE) and 2 reports of deep vein thrombosis (DVT) occurring during or soon after treatment with the CELLEX Photopheresis System.

Two of the patients who developed a PE died, although it’s not clear whether PE was the cause of death.

Four of the 7 PEs occurred in patients undergoing treatment for GVHD, including the 2 patients who died. Both DVTs occurred in patients undergoing treatment for GVHD as well.

The FDA is recommending that healthcare providers inform patients, clinical staff, and technicians that PE and DVT can occur during or after an ECP procedure.

The agency also recommends that healthcare providers consult device labeling regarding anticoagulation and use clinical judgment in adjusting a patient’s heparin dosage.

Finally, providers should report VTEs related to ECP procedures to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.

If possible, reports should include the following:

• The indication for ECP therapy
• Comorbidities that may predispose a patient to increased coagulation and history of DVT or PE
• The anticoagulation regimen used
• The number of ECP sessions the patient underwent prior to VTE onset, including the date of the first treatment session, frequency of treatment sessions, and timing of the final treatment
• Timing of the VTE in relation to the most recent treatment session
• Interventions required to manage the VTE.
  

Red and white blood cells

The US Food and Drug Administration (FDA) says it is evaluating reports of venous thromboembolism (VTE) in patients treated with the CELLEX Photopheresis System by Therakos, Inc.

This extracorporeal photopheresis (ECP) device system is FDA-approved for use in patients with cutaneous T-cell lymphoma (CTCL).

The system is used to perform ultraviolet-A irradiation of a patient’s own leukocyte-enriched blood that is then used as palliative treatment for skin manifestations of CTCL that are unresponsive to other forms of treatment.

The CELLEX Photopheresis System is also used to treat graft-vs-host disease (GVHD) that is resistant to standard immunosuppressive therapy and acute cardiac allograft rejection that is resistant to standard immunosuppressive therapy.

The CELLEX Photopheresis System uses methoxsalen as a photosensitizing agent and heparin as an anticoagulant.

Since 2012, the FDA has received 7 reports of pulmonary embolism (PE) and 2 reports of deep vein thrombosis (DVT) occurring during or soon after treatment with the CELLEX Photopheresis System.

Two of the patients who developed a PE died, although it’s not clear whether PE was the cause of death.

Four of the 7 PEs occurred in patients undergoing treatment for GVHD, including the 2 patients who died. Both DVTs occurred in patients undergoing treatment for GVHD as well.

The FDA is recommending that healthcare providers inform patients, clinical staff, and technicians that PE and DVT can occur during or after an ECP procedure.

The agency also recommends that healthcare providers consult device labeling regarding anticoagulation and use clinical judgment in adjusting a patient’s heparin dosage.

Finally, providers should report VTEs related to ECP procedures to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.

If possible, reports should include the following:

• The indication for ECP therapy
• Comorbidities that may predispose a patient to increased coagulation and history of DVT or PE
• The anticoagulation regimen used
• The number of ECP sessions the patient underwent prior to VTE onset, including the date of the first treatment session, frequency of treatment sessions, and timing of the final treatment
• Timing of the VTE in relation to the most recent treatment session
• Interventions required to manage the VTE.
  

Red and white blood cells

The US Food and Drug Administration (FDA) says it is evaluating reports of venous thromboembolism (VTE) in patients treated with the CELLEX Photopheresis System by Therakos, Inc.

This extracorporeal photopheresis (ECP) device system is FDA-approved for use in patients with cutaneous T-cell lymphoma (CTCL).

The system is used to perform ultraviolet-A irradiation of a patient’s own leukocyte-enriched blood that is then used as palliative treatment for skin manifestations of CTCL that are unresponsive to other forms of treatment.

The CELLEX Photopheresis System is also used to treat graft-vs-host disease (GVHD) that is resistant to standard immunosuppressive therapy and acute cardiac allograft rejection that is resistant to standard immunosuppressive therapy.

The CELLEX Photopheresis System uses methoxsalen as a photosensitizing agent and heparin as an anticoagulant.

Since 2012, the FDA has received 7 reports of pulmonary embolism (PE) and 2 reports of deep vein thrombosis (DVT) occurring during or soon after treatment with the CELLEX Photopheresis System.

Two of the patients who developed a PE died, although it’s not clear whether PE was the cause of death.

Four of the 7 PEs occurred in patients undergoing treatment for GVHD, including the 2 patients who died. Both DVTs occurred in patients undergoing treatment for GVHD as well.

The FDA is recommending that healthcare providers inform patients, clinical staff, and technicians that PE and DVT can occur during or after an ECP procedure.

The agency also recommends that healthcare providers consult device labeling regarding anticoagulation and use clinical judgment in adjusting a patient’s heparin dosage.

Finally, providers should report VTEs related to ECP procedures to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.

If possible, reports should include the following:

• The indication for ECP therapy
• Comorbidities that may predispose a patient to increased coagulation and history of DVT or PE
• The anticoagulation regimen used
• The number of ECP sessions the patient underwent prior to VTE onset, including the date of the first treatment session, frequency of treatment sessions, and timing of the final treatment
• Timing of the VTE in relation to the most recent treatment session
• Interventions required to manage the VTE.
  

An international prognostic index for patients with chronic lymphocytic leukemia (CLL), known as CLL-IPI, was predictive of time from diagnosis to first treatment (TTFT) and 5-year median overall survival in patients across different risk categories treated with chemoimmunotherapy, according to a systematic review and meta-analysis published in Blood (2018 Jan 18;131[3]:365-8).

But limited data were available for patients treated with targeted therapies that are likely to have a profound effect on overall survival; thereby restricting the use of CLL-IPI in current clinical practice.

Novel therapies such as ibrutinib, idelalisib, and venetoclax have changed the treatment landscape for CLL, Stefano Molica, MD, of Azienda Ospedaliera Pugliese-Ciaccio, Catanzaro, Italy, and his colleagues wrote. “Because observation remains the standard of care for asymptomatic early-stage patients, the introduction of these agents does not impact the utility of the CLL-IPI for predicting time from diagnosis to first treatment, but it likely has a profound impact on the survival of patients of all risk categories once treatment is indicated.”

The CLL-IPI tool, first published in 2016 to predict clinical outcomes in CLL patients, combines five parameters: age, clinical stage, TP53 status [normal vs. del(17p) and/or TP53 mutation], immunoglobulin heavy chain–variable mutational status, and serum b2-microglobulin. The prognostic tool was validated across several studies conducted in different countries with diverse practice settings, including academic hospitals, national population-based cohorts, and clinical trials.

The researchers conducted a systematic review and meta-analysis to understand the utility of CLL-IPI tool in predicting OS and TTFT across each risk category of CLL patients.

They included nine studies with 7,843 patients to assess the impact of the CLL-IPI on overall survival. The patient distribution into the CLL-IPI risk categories was low risk (median 45.9%), intermediate risk (median 30%), high risk (median 16.5%), and very high risk (median 3.6%).

The researchers relied on 11 series comprising 7,383 patients to assess 5-year survival probability, which was 92% for low risk, 81% for intermediate risk, 60% for high risk, and 34% for very high risk. They used seven studies comprising 5,206 patients to assess TTFT and found that the probability of remaining treatment free at 5 years was 82% in the low-risk group, 45% in the intermediate-risk group, 30% in the high-risk group, and 16% in the very-high-risk group.

Although a significant step toward harmonizing international prognostication for CLL, additional studies validating the utility of the CLL-IPI for predicting OS in patients treated with targeted therapy are needed, they wrote.

The researchers reported having no financial disclosures.

hematologynews@frontlinemedcom.com

An international prognostic index for patients with chronic lymphocytic leukemia (CLL), known as CLL-IPI, was predictive of time from diagnosis to first treatment (TTFT) and 5-year median overall survival in patients across different risk categories treated with chemoimmunotherapy, according to a systematic review and meta-analysis published in Blood (2018 Jan 18;131[3]:365-8).

But limited data were available for patients treated with targeted therapies that are likely to have a profound effect on overall survival; thereby restricting the use of CLL-IPI in current clinical practice.

Novel therapies such as ibrutinib, idelalisib, and venetoclax have changed the treatment landscape for CLL, Stefano Molica, MD, of Azienda Ospedaliera Pugliese-Ciaccio, Catanzaro, Italy, and his colleagues wrote. “Because observation remains the standard of care for asymptomatic early-stage patients, the introduction of these agents does not impact the utility of the CLL-IPI for predicting time from diagnosis to first treatment, but it likely has a profound impact on the survival of patients of all risk categories once treatment is indicated.”

The CLL-IPI tool, first published in 2016 to predict clinical outcomes in CLL patients, combines five parameters: age, clinical stage, TP53 status [normal vs. del(17p) and/or TP53 mutation], immunoglobulin heavy chain–variable mutational status, and serum b2-microglobulin. The prognostic tool was validated across several studies conducted in different countries with diverse practice settings, including academic hospitals, national population-based cohorts, and clinical trials.

The researchers conducted a systematic review and meta-analysis to understand the utility of CLL-IPI tool in predicting OS and TTFT across each risk category of CLL patients.

They included nine studies with 7,843 patients to assess the impact of the CLL-IPI on overall survival. The patient distribution into the CLL-IPI risk categories was low risk (median 45.9%), intermediate risk (median 30%), high risk (median 16.5%), and very high risk (median 3.6%).

The researchers relied on 11 series comprising 7,383 patients to assess 5-year survival probability, which was 92% for low risk, 81% for intermediate risk, 60% for high risk, and 34% for very high risk. They used seven studies comprising 5,206 patients to assess TTFT and found that the probability of remaining treatment free at 5 years was 82% in the low-risk group, 45% in the intermediate-risk group, 30% in the high-risk group, and 16% in the very-high-risk group.

Although a significant step toward harmonizing international prognostication for CLL, additional studies validating the utility of the CLL-IPI for predicting OS in patients treated with targeted therapy are needed, they wrote.

The researchers reported having no financial disclosures.

hematologynews@frontlinemedcom.com

An international prognostic index for patients with chronic lymphocytic leukemia (CLL), known as CLL-IPI, was predictive of time from diagnosis to first treatment (TTFT) and 5-year median overall survival in patients across different risk categories treated with chemoimmunotherapy, according to a systematic review and meta-analysis published in Blood (2018 Jan 18;131[3]:365-8).

But limited data were available for patients treated with targeted therapies that are likely to have a profound effect on overall survival; thereby restricting the use of CLL-IPI in current clinical practice.

Novel therapies such as ibrutinib, idelalisib, and venetoclax have changed the treatment landscape for CLL, Stefano Molica, MD, of Azienda Ospedaliera Pugliese-Ciaccio, Catanzaro, Italy, and his colleagues wrote. “Because observation remains the standard of care for asymptomatic early-stage patients, the introduction of these agents does not impact the utility of the CLL-IPI for predicting time from diagnosis to first treatment, but it likely has a profound impact on the survival of patients of all risk categories once treatment is indicated.”

The CLL-IPI tool, first published in 2016 to predict clinical outcomes in CLL patients, combines five parameters: age, clinical stage, TP53 status [normal vs. del(17p) and/or TP53 mutation], immunoglobulin heavy chain–variable mutational status, and serum b2-microglobulin. The prognostic tool was validated across several studies conducted in different countries with diverse practice settings, including academic hospitals, national population-based cohorts, and clinical trials.

The researchers conducted a systematic review and meta-analysis to understand the utility of CLL-IPI tool in predicting OS and TTFT across each risk category of CLL patients.

They included nine studies with 7,843 patients to assess the impact of the CLL-IPI on overall survival. The patient distribution into the CLL-IPI risk categories was low risk (median 45.9%), intermediate risk (median 30%), high risk (median 16.5%), and very high risk (median 3.6%).

The researchers relied on 11 series comprising 7,383 patients to assess 5-year survival probability, which was 92% for low risk, 81% for intermediate risk, 60% for high risk, and 34% for very high risk. They used seven studies comprising 5,206 patients to assess TTFT and found that the probability of remaining treatment free at 5 years was 82% in the low-risk group, 45% in the intermediate-risk group, 30% in the high-risk group, and 16% in the very-high-risk group.

Although a significant step toward harmonizing international prognostication for CLL, additional studies validating the utility of the CLL-IPI for predicting OS in patients treated with targeted therapy are needed, they wrote.

The researchers reported having no financial disclosures.

hematologynews@frontlinemedcom.com

Photo by Larry Young

LA JOLLA, CA—Mogamulizumab is a valuable new therapeutic option for patients with cutaneous T-cell lymphoma (CTCL), according to researchers.

Results of the phase 3 MAVORIC study indicated that mogamulizumab is more effective than vorinostat in previously treated patients with CTCL.

Mogamulizumab produced a better overall response rate (ORR) and prolonged progression-free survival (PFS) in these patients.

Infusion-related reactions and drug eruptions were more common in patients who received mogamulizumab.

Youn H. Kim, MD, of the Stanford Cancer Institute in Palo Alto, California, and her colleagues presented these results in a poster at the 10th Annual T-cell Lymphoma Forum. The study was funded by Kyowa Kirin Pharmaceutical Development, Inc.

MAVORIC enrolled 372 adults with histologically confirmed mycosis fungoides (MF) or Sézary syndrome (SS) who had failed at least 1 systemic therapy. They were randomized to receive mogamulizumab at 1.0 mg/kg (weekly for the first 4-week cycle and then every 2 weeks) or vorinostat at 400 mg daily.

Patients were treated until disease progression or unacceptable toxicity. Those receiving vorinostat could crossover to mogamulizumab if they progressed or experienced intolerable toxicity.

Baseline characteristics were similar between the treatment arms. The median age was 64 (range, 54-73) in the mogamulizumab arm and 65 (range, 56-72) in the vorinostat arm. Ninety-nine percent and 100% of patients, respectively, had an ECOG performance status of 0 to 1.

A little more than half of patients in each arm had MF—57% in the mogamulizumab arm and 53% in the vorinostat arm.

The median number of prior systemic therapies was 3 in both arms (range, 1-18 in the mogamulizumab arm and 0-14 in the vorinostat arm).

Efficacy

The primary endpoint was PFS, and mogamulizumab provided a significant improvement there. The median PFS was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio=0.53, P<0.0001).

The researchers also observed a significant improvement in global ORR with mogamulizumab. It was 28% (52/189) in that arm and 5% (9/186) in the vorinostat arm (P<0.0001).

For patients with MF, the ORR was 21% with mogamulizumab and 7% with vorinostat. For SS patients, the ORR was 37% and 2%, respectively.

Responses by disease compartment were superior with mogamulizumab as well.

“Especially in the blood compartment, mogamulizumab had very striking activity over vorinostat,” Dr Kim said.

The blood ORR was 68% with mogamulizumab and 19% with vorinostat. The skin ORR was 42% and 16%, respectively. The lymph node ORR was 17% and 4%, respectively. The viscera ORR was 0% in both arms.

After crossover, the ORR in the mogamulizumab arm was 30% (41/136).

The median duration of response (DOR) was 14 months in the mogamulizumab arm and 9 months in the vorinostat arm.

For MF patients, the median DOR was 13 months with mogamulizumab and 9 months with vorinostat. For SS patients, the median DOR was 17 months and 7 months, respectively.

Safety

“Side effects [of mogamulizumab] were very well tolerable,” Dr Kim said. “Most significant is rash and infusion reactions, but, in terms of severe adverse events, [they] were very minimal.”

The most common treatment-emergent adverse events (AEs), occurring in at least 20% of patients in either arm (mogamulizumab and vorinostat, respectively), were:

• Infusion-related reactions (33.2% vs 0.5%)
• Drug eruptions (23.9% vs 0.5%)
• Diarrhea (23.4% vs 61.8%)
• Nausea (15.2% vs 42.5%)
• Thrombocytopenia (11.4% vs 30.6%)
• Dysgeusia (3.3% vs 28.0%)
• Increased blood creatinine (3.3% vs 28.0%)
• Decreased appetite (7.6% vs 24.7%).

There were no grade 4 AEs in the mogamulizumab arm and 2 cases of grade 4 thrombocytopenia in the vorinostat arm.

Grade 3 AEs in the mogamulizumab arm included drug eruptions (n=8), infusion-related reactions (n=3), fatigue (n=3), decreased appetite (n=2), nausea (n=1), pyrexia (n=1), and diarrhea (n=1).

Grade 3 AEs in the vorinostat arm included thrombocytopenia (n=11), fatigue (n=11), diarrhea (n=9), nausea (n=3), decreased appetite (n=2), and dysgeusia (n=1).

“So the results are, overall, positive,” Dr Kim said. “The data is submitted to the [US Food and Drug Administration]. We are really hoping that [mogamulizumab] will be approved so that we would have a new, exciting treatment for our patients with mycosis fungoides and Sézary syndrome.”

Photo by Larry Young

LA JOLLA, CA—Mogamulizumab is a valuable new therapeutic option for patients with cutaneous T-cell lymphoma (CTCL), according to researchers.

Results of the phase 3 MAVORIC study indicated that mogamulizumab is more effective than vorinostat in previously treated patients with CTCL.

Mogamulizumab produced a better overall response rate (ORR) and prolonged progression-free survival (PFS) in these patients.

Infusion-related reactions and drug eruptions were more common in patients who received mogamulizumab.

Youn H. Kim, MD, of the Stanford Cancer Institute in Palo Alto, California, and her colleagues presented these results in a poster at the 10th Annual T-cell Lymphoma Forum. The study was funded by Kyowa Kirin Pharmaceutical Development, Inc.

MAVORIC enrolled 372 adults with histologically confirmed mycosis fungoides (MF) or Sézary syndrome (SS) who had failed at least 1 systemic therapy. They were randomized to receive mogamulizumab at 1.0 mg/kg (weekly for the first 4-week cycle and then every 2 weeks) or vorinostat at 400 mg daily.

Patients were treated until disease progression or unacceptable toxicity. Those receiving vorinostat could crossover to mogamulizumab if they progressed or experienced intolerable toxicity.

Baseline characteristics were similar between the treatment arms. The median age was 64 (range, 54-73) in the mogamulizumab arm and 65 (range, 56-72) in the vorinostat arm. Ninety-nine percent and 100% of patients, respectively, had an ECOG performance status of 0 to 1.

A little more than half of patients in each arm had MF—57% in the mogamulizumab arm and 53% in the vorinostat arm.

The median number of prior systemic therapies was 3 in both arms (range, 1-18 in the mogamulizumab arm and 0-14 in the vorinostat arm).

Efficacy

The primary endpoint was PFS, and mogamulizumab provided a significant improvement there. The median PFS was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio=0.53, P<0.0001).

The researchers also observed a significant improvement in global ORR with mogamulizumab. It was 28% (52/189) in that arm and 5% (9/186) in the vorinostat arm (P<0.0001).

For patients with MF, the ORR was 21% with mogamulizumab and 7% with vorinostat. For SS patients, the ORR was 37% and 2%, respectively.

Responses by disease compartment were superior with mogamulizumab as well.

“Especially in the blood compartment, mogamulizumab had very striking activity over vorinostat,” Dr Kim said.

The blood ORR was 68% with mogamulizumab and 19% with vorinostat. The skin ORR was 42% and 16%, respectively. The lymph node ORR was 17% and 4%, respectively. The viscera ORR was 0% in both arms.

After crossover, the ORR in the mogamulizumab arm was 30% (41/136).

The median duration of response (DOR) was 14 months in the mogamulizumab arm and 9 months in the vorinostat arm.

For MF patients, the median DOR was 13 months with mogamulizumab and 9 months with vorinostat. For SS patients, the median DOR was 17 months and 7 months, respectively.

Safety

“Side effects [of mogamulizumab] were very well tolerable,” Dr Kim said. “Most significant is rash and infusion reactions, but, in terms of severe adverse events, [they] were very minimal.”

The most common treatment-emergent adverse events (AEs), occurring in at least 20% of patients in either arm (mogamulizumab and vorinostat, respectively), were:

• Infusion-related reactions (33.2% vs 0.5%)
• Drug eruptions (23.9% vs 0.5%)
• Diarrhea (23.4% vs 61.8%)
• Nausea (15.2% vs 42.5%)
• Thrombocytopenia (11.4% vs 30.6%)
• Dysgeusia (3.3% vs 28.0%)
• Increased blood creatinine (3.3% vs 28.0%)
• Decreased appetite (7.6% vs 24.7%).

There were no grade 4 AEs in the mogamulizumab arm and 2 cases of grade 4 thrombocytopenia in the vorinostat arm.

Grade 3 AEs in the mogamulizumab arm included drug eruptions (n=8), infusion-related reactions (n=3), fatigue (n=3), decreased appetite (n=2), nausea (n=1), pyrexia (n=1), and diarrhea (n=1).

Grade 3 AEs in the vorinostat arm included thrombocytopenia (n=11), fatigue (n=11), diarrhea (n=9), nausea (n=3), decreased appetite (n=2), and dysgeusia (n=1).

“So the results are, overall, positive,” Dr Kim said. “The data is submitted to the [US Food and Drug Administration]. We are really hoping that [mogamulizumab] will be approved so that we would have a new, exciting treatment for our patients with mycosis fungoides and Sézary syndrome.”

Photo by Larry Young

LA JOLLA, CA—Mogamulizumab is a valuable new therapeutic option for patients with cutaneous T-cell lymphoma (CTCL), according to researchers.

Results of the phase 3 MAVORIC study indicated that mogamulizumab is more effective than vorinostat in previously treated patients with CTCL.

Mogamulizumab produced a better overall response rate (ORR) and prolonged progression-free survival (PFS) in these patients.

Infusion-related reactions and drug eruptions were more common in patients who received mogamulizumab.

Youn H. Kim, MD, of the Stanford Cancer Institute in Palo Alto, California, and her colleagues presented these results in a poster at the 10th Annual T-cell Lymphoma Forum. The study was funded by Kyowa Kirin Pharmaceutical Development, Inc.

MAVORIC enrolled 372 adults with histologically confirmed mycosis fungoides (MF) or Sézary syndrome (SS) who had failed at least 1 systemic therapy. They were randomized to receive mogamulizumab at 1.0 mg/kg (weekly for the first 4-week cycle and then every 2 weeks) or vorinostat at 400 mg daily.

Patients were treated until disease progression or unacceptable toxicity. Those receiving vorinostat could crossover to mogamulizumab if they progressed or experienced intolerable toxicity.

Baseline characteristics were similar between the treatment arms. The median age was 64 (range, 54-73) in the mogamulizumab arm and 65 (range, 56-72) in the vorinostat arm. Ninety-nine percent and 100% of patients, respectively, had an ECOG performance status of 0 to 1.

A little more than half of patients in each arm had MF—57% in the mogamulizumab arm and 53% in the vorinostat arm.

The median number of prior systemic therapies was 3 in both arms (range, 1-18 in the mogamulizumab arm and 0-14 in the vorinostat arm).

Efficacy

The primary endpoint was PFS, and mogamulizumab provided a significant improvement there. The median PFS was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio=0.53, P<0.0001).

The researchers also observed a significant improvement in global ORR with mogamulizumab. It was 28% (52/189) in that arm and 5% (9/186) in the vorinostat arm (P<0.0001).

For patients with MF, the ORR was 21% with mogamulizumab and 7% with vorinostat. For SS patients, the ORR was 37% and 2%, respectively.

Responses by disease compartment were superior with mogamulizumab as well.

“Especially in the blood compartment, mogamulizumab had very striking activity over vorinostat,” Dr Kim said.

The blood ORR was 68% with mogamulizumab and 19% with vorinostat. The skin ORR was 42% and 16%, respectively. The lymph node ORR was 17% and 4%, respectively. The viscera ORR was 0% in both arms.

After crossover, the ORR in the mogamulizumab arm was 30% (41/136).

The median duration of response (DOR) was 14 months in the mogamulizumab arm and 9 months in the vorinostat arm.

For MF patients, the median DOR was 13 months with mogamulizumab and 9 months with vorinostat. For SS patients, the median DOR was 17 months and 7 months, respectively.

Safety

“Side effects [of mogamulizumab] were very well tolerable,” Dr Kim said. “Most significant is rash and infusion reactions, but, in terms of severe adverse events, [they] were very minimal.”

The most common treatment-emergent adverse events (AEs), occurring in at least 20% of patients in either arm (mogamulizumab and vorinostat, respectively), were:

• Infusion-related reactions (33.2% vs 0.5%)
• Drug eruptions (23.9% vs 0.5%)
• Diarrhea (23.4% vs 61.8%)
• Nausea (15.2% vs 42.5%)
• Thrombocytopenia (11.4% vs 30.6%)
• Dysgeusia (3.3% vs 28.0%)
• Increased blood creatinine (3.3% vs 28.0%)
• Decreased appetite (7.6% vs 24.7%).

There were no grade 4 AEs in the mogamulizumab arm and 2 cases of grade 4 thrombocytopenia in the vorinostat arm.

Grade 3 AEs in the mogamulizumab arm included drug eruptions (n=8), infusion-related reactions (n=3), fatigue (n=3), decreased appetite (n=2), nausea (n=1), pyrexia (n=1), and diarrhea (n=1).

Grade 3 AEs in the vorinostat arm included thrombocytopenia (n=11), fatigue (n=11), diarrhea (n=9), nausea (n=3), decreased appetite (n=2), and dysgeusia (n=1).

“So the results are, overall, positive,” Dr Kim said. “The data is submitted to the [US Food and Drug Administration]. We are really hoping that [mogamulizumab] will be approved so that we would have a new, exciting treatment for our patients with mycosis fungoides and Sézary syndrome.”

A combination of ibrutinib, lenalidomide, and rituximab produced an overall response rate of 76% at 17.8 months median follow-up among 50 adults with relapsed or refractory mantle cell lymphoma, according to an open-label, single-arm, phase 2 trial.

There were complete responses in 28 patients (56%) and partial responses in 10 (20%). Median progression-free survival was 16 months and median overall survival was 22 months. Similar proportions of patients, with and without TP53 mutations, had overall and complete responses, suggesting that triple therapy might be particularly useful in patients with high-risk genetic features.

“Our results provide preliminary evidence that the triplet combination of ibrutinib, lenalidomide, and rituximab is an active regimen in patients with relapsed or refractory mantle cell lymphoma, and should be evaluated in a prospective randomized controlled trial,” wrote Mats Jerkeman, MD, of Lund University, Sweden, and colleagues. The report was published in The Lancet Haematology.

“Addition of lenalidomide to ibrutinib and rituximab might increase the proportion of patients who have complete remission ... Previous studies reported complete responses in 44% of patients on ibrutinib and rituximab, in 36% of patients on rituximab and lenalidomide, and in 19% of patients on ibrutinib alone,” they wrote.

Courtesy Wikimedia Commons/Nephron/Creative Commons

aotto@frontlinemedcom.com

SOURCE: Jerkeman M et al. Lancet Haematol. 2018 Jan 29. doi: 10.1016/S2352-3026(18)30018-8.

A combination of ibrutinib, lenalidomide, and rituximab produced an overall response rate of 76% at 17.8 months median follow-up among 50 adults with relapsed or refractory mantle cell lymphoma, according to an open-label, single-arm, phase 2 trial.

There were complete responses in 28 patients (56%) and partial responses in 10 (20%). Median progression-free survival was 16 months and median overall survival was 22 months. Similar proportions of patients, with and without TP53 mutations, had overall and complete responses, suggesting that triple therapy might be particularly useful in patients with high-risk genetic features.

“Our results provide preliminary evidence that the triplet combination of ibrutinib, lenalidomide, and rituximab is an active regimen in patients with relapsed or refractory mantle cell lymphoma, and should be evaluated in a prospective randomized controlled trial,” wrote Mats Jerkeman, MD, of Lund University, Sweden, and colleagues. The report was published in The Lancet Haematology.

“Addition of lenalidomide to ibrutinib and rituximab might increase the proportion of patients who have complete remission ... Previous studies reported complete responses in 44% of patients on ibrutinib and rituximab, in 36% of patients on rituximab and lenalidomide, and in 19% of patients on ibrutinib alone,” they wrote.

Courtesy Wikimedia Commons/Nephron/Creative Commons

aotto@frontlinemedcom.com

SOURCE: Jerkeman M et al. Lancet Haematol. 2018 Jan 29. doi: 10.1016/S2352-3026(18)30018-8.

A combination of ibrutinib, lenalidomide, and rituximab produced an overall response rate of 76% at 17.8 months median follow-up among 50 adults with relapsed or refractory mantle cell lymphoma, according to an open-label, single-arm, phase 2 trial.

There were complete responses in 28 patients (56%) and partial responses in 10 (20%). Median progression-free survival was 16 months and median overall survival was 22 months. Similar proportions of patients, with and without TP53 mutations, had overall and complete responses, suggesting that triple therapy might be particularly useful in patients with high-risk genetic features.

“Our results provide preliminary evidence that the triplet combination of ibrutinib, lenalidomide, and rituximab is an active regimen in patients with relapsed or refractory mantle cell lymphoma, and should be evaluated in a prospective randomized controlled trial,” wrote Mats Jerkeman, MD, of Lund University, Sweden, and colleagues. The report was published in The Lancet Haematology.

“Addition of lenalidomide to ibrutinib and rituximab might increase the proportion of patients who have complete remission ... Previous studies reported complete responses in 44% of patients on ibrutinib and rituximab, in 36% of patients on rituximab and lenalidomide, and in 19% of patients on ibrutinib alone,” they wrote.

Courtesy Wikimedia Commons/Nephron/Creative Commons

aotto@frontlinemedcom.com

SOURCE: Jerkeman M et al. Lancet Haematol. 2018 Jan 29. doi: 10.1016/S2352-3026(18)30018-8.