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FDA approves betrixaban for VTE prophylaxis
Betrixaban, a factor Xa inhibitor, has been approved for the prophylaxis of venous thromboembolism (VTE) in at-risk adult patients hospitalized with an acute illness, according to an announcement from the Food and Drug Administration.
Approval was based on results from a randomized, double-blind clinical trial in which over 7,000 hospitalized patients at risk for VTE received either extended-duration betrixaban (35-42 days) or short duration enoxaparin (6-14 days), a low molecular weight heparin administered subcutaneously. The rate of deep vein thrombosis, nonfatal pulmonary embolism, or VTE-related death was 4.4% among patients receiving betrixaban and 6% among patients receiving enoxaparin (relative risk, 0.75; 95% confidence interval: 0.61, 0.91).
The recommended dosage for betrixaban is 80 mg per day for 35-42 days at the same time every day with food, after a dose of 160 mg on the first day of treatment.
Betrixaban will be marketed as Bevyxxa by Portola.
Find the full FDA announcement and prescribing information on the FDA website.
Betrixaban, a factor Xa inhibitor, has been approved for the prophylaxis of venous thromboembolism (VTE) in at-risk adult patients hospitalized with an acute illness, according to an announcement from the Food and Drug Administration.
Approval was based on results from a randomized, double-blind clinical trial in which over 7,000 hospitalized patients at risk for VTE received either extended-duration betrixaban (35-42 days) or short duration enoxaparin (6-14 days), a low molecular weight heparin administered subcutaneously. The rate of deep vein thrombosis, nonfatal pulmonary embolism, or VTE-related death was 4.4% among patients receiving betrixaban and 6% among patients receiving enoxaparin (relative risk, 0.75; 95% confidence interval: 0.61, 0.91).
The recommended dosage for betrixaban is 80 mg per day for 35-42 days at the same time every day with food, after a dose of 160 mg on the first day of treatment.
Betrixaban will be marketed as Bevyxxa by Portola.
Find the full FDA announcement and prescribing information on the FDA website.
Betrixaban, a factor Xa inhibitor, has been approved for the prophylaxis of venous thromboembolism (VTE) in at-risk adult patients hospitalized with an acute illness, according to an announcement from the Food and Drug Administration.
Approval was based on results from a randomized, double-blind clinical trial in which over 7,000 hospitalized patients at risk for VTE received either extended-duration betrixaban (35-42 days) or short duration enoxaparin (6-14 days), a low molecular weight heparin administered subcutaneously. The rate of deep vein thrombosis, nonfatal pulmonary embolism, or VTE-related death was 4.4% among patients receiving betrixaban and 6% among patients receiving enoxaparin (relative risk, 0.75; 95% confidence interval: 0.61, 0.91).
The recommended dosage for betrixaban is 80 mg per day for 35-42 days at the same time every day with food, after a dose of 160 mg on the first day of treatment.
Betrixaban will be marketed as Bevyxxa by Portola.
Find the full FDA announcement and prescribing information on the FDA website.
Twofer drug blocks SYK/JAK pathways in advanced NHL
MADRID – Cerdulatinib, a single oral agent targeting two different pathways that lymphomas rely on for survival, produced rapid tumor responses in patients with relapsed or refractory non-Hodgkin lymphomas (NHL) in a phase II study.
The overall response rate among 47 patients enrolled in a phase II study was 50%, including responses among 67% of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and 56% of patients with follicular lymphoma (FL), reported Paul A. Hamlin, MD, of the Memorial Sloan Kettering Cancer Center in New York.
“At a dose of 30 mg b.i.d., cerdulatinib inhibited pathways of interest, so both SYK and JAK are inhibited at maximum amounts at physiologically attained doses,” he said at a briefing at the annual congress of the European Hematology Association.
Certain B cell malignancies are “addicted” to B cell antigen-receptor (BCR) signaling. A combination of selective SYK and JAK inhibitors can syngergistically suppress this response in B cell malignancies, he said.
In a phase I dose escalation study of cerdulatinib in 43 patients with relapsed/refractory CLL and NHL reported by Dr. Hamlin and his colleagues at the 2016 EHA annual congress, inhibition with cerdulatinib of both the BCR/SYK and JAK/STAT pathways in peripheral blood assays was well tolerated.
In the current phase II, multicenter, open-label study, the investigators plan on enrolling up to 40 patients in each of three cohorts: relapsed refractory CLL/SLL, relapsed/refractory indolent NHL, and relapsed diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma (MCL) and transformed FL. The investigators have also begun to enroll patients with peripheral T-cell lymphoma (PTCL) based on efficacy of the dual pathway inhibitor against this malignancy.
The patients received 30-mg cerdulatinib orally twice daily until disease progression or intolerable toxicity.
As noted, the overall response rate was 50% (47 patients), including partial responses (PR) in 12 of 18 (67%) of patients with CLL/SLL, in five of nine patients (56%) with FL, and in one of seven patients with relapsed refractory marginal zone lymphoma and Waldenstrom macroglobulinemia.
In addition, the investigators identified one complete response in the first enrolled patient with PTCL.
“I think this is a proof of principle that the biology suggesting that SYK is expressed in T-cell lymphomas and may have an important role in its pathogenesis holds true,” Dr. Hamlin said.
Responses have been detected in heavily pretreated patients, including one patient with FL who had a relapse on ibrutinib and a patient with SLL who had a relapse during treatment with venetoclax. Both patients remain on cerdulatinib after 10 months. At the time of the data presentation, 15 patients are continuing therapy with the dual inhibitor, including 4 who have been taking it for more than 300 days.
The responses occurred after a median of two cycles, Dr. Hamlin noted, and improved over time, as seen in seven of nine patients with increased reduction of nodal masses at the second or third rescan.
The most frequent adverse events with cerdulatinib at the target dose of 30 mg are fatigue, diarrhea, nausea, and cytopenias.
In the dose-escalation phase, three patients at a dose of 35 mg b.i.d. had higher than expected drug concentrations and experienced severe adverse events, including two fatal infections and one grade 3 pancreatitis. The investigators launched a pharmacokinetics monitoring strategy in hopes of avoiding this complication in the future.
Dr. Hamlin said the efficacy to date suggests the cerdulatinib could be used as a single agent but added that its generally favorable safety profile may make it a good partner in combination therapies.
The study is supported by Molecular Templates. Dr. Hamlin disclosed grant/research support and/or consultant role for Spectrum, GlaxoSmithKline, Pfizer, Seattle Genetics, Genentech, and Gilead.
MADRID – Cerdulatinib, a single oral agent targeting two different pathways that lymphomas rely on for survival, produced rapid tumor responses in patients with relapsed or refractory non-Hodgkin lymphomas (NHL) in a phase II study.
The overall response rate among 47 patients enrolled in a phase II study was 50%, including responses among 67% of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and 56% of patients with follicular lymphoma (FL), reported Paul A. Hamlin, MD, of the Memorial Sloan Kettering Cancer Center in New York.
“At a dose of 30 mg b.i.d., cerdulatinib inhibited pathways of interest, so both SYK and JAK are inhibited at maximum amounts at physiologically attained doses,” he said at a briefing at the annual congress of the European Hematology Association.
Certain B cell malignancies are “addicted” to B cell antigen-receptor (BCR) signaling. A combination of selective SYK and JAK inhibitors can syngergistically suppress this response in B cell malignancies, he said.
In a phase I dose escalation study of cerdulatinib in 43 patients with relapsed/refractory CLL and NHL reported by Dr. Hamlin and his colleagues at the 2016 EHA annual congress, inhibition with cerdulatinib of both the BCR/SYK and JAK/STAT pathways in peripheral blood assays was well tolerated.
In the current phase II, multicenter, open-label study, the investigators plan on enrolling up to 40 patients in each of three cohorts: relapsed refractory CLL/SLL, relapsed/refractory indolent NHL, and relapsed diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma (MCL) and transformed FL. The investigators have also begun to enroll patients with peripheral T-cell lymphoma (PTCL) based on efficacy of the dual pathway inhibitor against this malignancy.
The patients received 30-mg cerdulatinib orally twice daily until disease progression or intolerable toxicity.
As noted, the overall response rate was 50% (47 patients), including partial responses (PR) in 12 of 18 (67%) of patients with CLL/SLL, in five of nine patients (56%) with FL, and in one of seven patients with relapsed refractory marginal zone lymphoma and Waldenstrom macroglobulinemia.
In addition, the investigators identified one complete response in the first enrolled patient with PTCL.
“I think this is a proof of principle that the biology suggesting that SYK is expressed in T-cell lymphomas and may have an important role in its pathogenesis holds true,” Dr. Hamlin said.
Responses have been detected in heavily pretreated patients, including one patient with FL who had a relapse on ibrutinib and a patient with SLL who had a relapse during treatment with venetoclax. Both patients remain on cerdulatinib after 10 months. At the time of the data presentation, 15 patients are continuing therapy with the dual inhibitor, including 4 who have been taking it for more than 300 days.
The responses occurred after a median of two cycles, Dr. Hamlin noted, and improved over time, as seen in seven of nine patients with increased reduction of nodal masses at the second or third rescan.
The most frequent adverse events with cerdulatinib at the target dose of 30 mg are fatigue, diarrhea, nausea, and cytopenias.
In the dose-escalation phase, three patients at a dose of 35 mg b.i.d. had higher than expected drug concentrations and experienced severe adverse events, including two fatal infections and one grade 3 pancreatitis. The investigators launched a pharmacokinetics monitoring strategy in hopes of avoiding this complication in the future.
Dr. Hamlin said the efficacy to date suggests the cerdulatinib could be used as a single agent but added that its generally favorable safety profile may make it a good partner in combination therapies.
The study is supported by Molecular Templates. Dr. Hamlin disclosed grant/research support and/or consultant role for Spectrum, GlaxoSmithKline, Pfizer, Seattle Genetics, Genentech, and Gilead.
MADRID – Cerdulatinib, a single oral agent targeting two different pathways that lymphomas rely on for survival, produced rapid tumor responses in patients with relapsed or refractory non-Hodgkin lymphomas (NHL) in a phase II study.
The overall response rate among 47 patients enrolled in a phase II study was 50%, including responses among 67% of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and 56% of patients with follicular lymphoma (FL), reported Paul A. Hamlin, MD, of the Memorial Sloan Kettering Cancer Center in New York.
“At a dose of 30 mg b.i.d., cerdulatinib inhibited pathways of interest, so both SYK and JAK are inhibited at maximum amounts at physiologically attained doses,” he said at a briefing at the annual congress of the European Hematology Association.
Certain B cell malignancies are “addicted” to B cell antigen-receptor (BCR) signaling. A combination of selective SYK and JAK inhibitors can syngergistically suppress this response in B cell malignancies, he said.
In a phase I dose escalation study of cerdulatinib in 43 patients with relapsed/refractory CLL and NHL reported by Dr. Hamlin and his colleagues at the 2016 EHA annual congress, inhibition with cerdulatinib of both the BCR/SYK and JAK/STAT pathways in peripheral blood assays was well tolerated.
In the current phase II, multicenter, open-label study, the investigators plan on enrolling up to 40 patients in each of three cohorts: relapsed refractory CLL/SLL, relapsed/refractory indolent NHL, and relapsed diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma (MCL) and transformed FL. The investigators have also begun to enroll patients with peripheral T-cell lymphoma (PTCL) based on efficacy of the dual pathway inhibitor against this malignancy.
The patients received 30-mg cerdulatinib orally twice daily until disease progression or intolerable toxicity.
As noted, the overall response rate was 50% (47 patients), including partial responses (PR) in 12 of 18 (67%) of patients with CLL/SLL, in five of nine patients (56%) with FL, and in one of seven patients with relapsed refractory marginal zone lymphoma and Waldenstrom macroglobulinemia.
In addition, the investigators identified one complete response in the first enrolled patient with PTCL.
“I think this is a proof of principle that the biology suggesting that SYK is expressed in T-cell lymphomas and may have an important role in its pathogenesis holds true,” Dr. Hamlin said.
Responses have been detected in heavily pretreated patients, including one patient with FL who had a relapse on ibrutinib and a patient with SLL who had a relapse during treatment with venetoclax. Both patients remain on cerdulatinib after 10 months. At the time of the data presentation, 15 patients are continuing therapy with the dual inhibitor, including 4 who have been taking it for more than 300 days.
The responses occurred after a median of two cycles, Dr. Hamlin noted, and improved over time, as seen in seven of nine patients with increased reduction of nodal masses at the second or third rescan.
The most frequent adverse events with cerdulatinib at the target dose of 30 mg are fatigue, diarrhea, nausea, and cytopenias.
In the dose-escalation phase, three patients at a dose of 35 mg b.i.d. had higher than expected drug concentrations and experienced severe adverse events, including two fatal infections and one grade 3 pancreatitis. The investigators launched a pharmacokinetics monitoring strategy in hopes of avoiding this complication in the future.
Dr. Hamlin said the efficacy to date suggests the cerdulatinib could be used as a single agent but added that its generally favorable safety profile may make it a good partner in combination therapies.
The study is supported by Molecular Templates. Dr. Hamlin disclosed grant/research support and/or consultant role for Spectrum, GlaxoSmithKline, Pfizer, Seattle Genetics, Genentech, and Gilead.
AT EHA 2017
Key clinical point: Cerdulatinib, an inhibitor of the SYK and JAK pathways, has shown efficacy against relapsed/refractory non-Hodgkin lymphomas.
Major finding: The overall response rate was 50%, including one complete response in a patient with peripheral T-cell lymphoma.
Data source: An open label, phase II study in 47 patients with non-Hodgkin lymphoma or peripheral T-cell lymphoma.
Disclosures: The study is supported by Molecular Templates. Dr. Hamlin disclosed grant/research support and/or consultant roles for Spectrum, GlaxoSmithKline, Pfizer, Seattle Genetics, Genentech, and Gilead.
ACIP approves new influenza vaccine recommendations
FROM AN ACIP MEETING
by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) after a lengthy debate over specifics regarding recommendations for pregnant women.
The proposed recommendation that sparked the debate would change the wording of the previous recommendation for pregnant women to receive a seasonal inactivated vaccine (IIV) to “any licensed, recommended, and age-appropriate, trivalent or quadrivalent IIV or RIV [recombinant influenza vaccine] may be used.”
“I think there’s a subtle, but important difference here between making what would appear to be an affirmative statement that RIV is safe in pregnant women, versus just staying silent on it, and saying ‘we’re not saying you shouldn’t use it, but we don’t have enough data to affirmatively say it is safe,’ ” said Cindy Pellegrini, senior vice president of Public Policy and Government Affairs at the March of Dimes Foundation.
In response, members of the committee pointed out that the responsibility of determining safety lies with the Food and Drug Administration, which has already licensed the Flublok trivalent vaccine with expectations that the quadrivalent vaccine soon will follow.
While Lisa Grohskopf, MD, MPH, medical officer of the influenza division of the CDC, did acknowledge that there were more data on the safety of inactivated influenza vaccines, she asserted to the committee that “the general overall safety profile of Flublok in comparison to inactivated vaccines is reassuring.”
“For example, one concern that arises is reactogenicity and inflammation. [In terms of] overall reactogenicity in the studies where Flublok and inactivated vaccines have been compared, rates of the adverse and systemic reactions were similar,” Dr. Grohskopf said.
A motion was made to change the wording of the recommendation; however, the motion was not passed, and the eventual vote on the approval was conducted.
The ACIP also voted unanimously to change the safe age limit noted in influenza guidelines for use of Afluria (IIV3) from 9 years and older to 5 years and older. A footnote saying that the ACIP recommends Afluria for children 9 years and older will be removed.
This change, which mirrors the licensing Afluria has with the FDA, was based on research conducted by Seqirus that showed fever levels were the same for Afluria trivalent and quadrivalent vaccines in children 5 to 9 years old, both of which were less than historical vaccine rates.
The approved recommendations will be sent to the director of the CDC and the U.S. Department of Health and Human Services. Once reviewed and approved, the final recommendations will be published in the CDC’s Morbidity and Mortality Weekly Report. The committee members had no relevant financial disclosures.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
FROM AN ACIP MEETING
by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) after a lengthy debate over specifics regarding recommendations for pregnant women.
The proposed recommendation that sparked the debate would change the wording of the previous recommendation for pregnant women to receive a seasonal inactivated vaccine (IIV) to “any licensed, recommended, and age-appropriate, trivalent or quadrivalent IIV or RIV [recombinant influenza vaccine] may be used.”
“I think there’s a subtle, but important difference here between making what would appear to be an affirmative statement that RIV is safe in pregnant women, versus just staying silent on it, and saying ‘we’re not saying you shouldn’t use it, but we don’t have enough data to affirmatively say it is safe,’ ” said Cindy Pellegrini, senior vice president of Public Policy and Government Affairs at the March of Dimes Foundation.
In response, members of the committee pointed out that the responsibility of determining safety lies with the Food and Drug Administration, which has already licensed the Flublok trivalent vaccine with expectations that the quadrivalent vaccine soon will follow.
While Lisa Grohskopf, MD, MPH, medical officer of the influenza division of the CDC, did acknowledge that there were more data on the safety of inactivated influenza vaccines, she asserted to the committee that “the general overall safety profile of Flublok in comparison to inactivated vaccines is reassuring.”
“For example, one concern that arises is reactogenicity and inflammation. [In terms of] overall reactogenicity in the studies where Flublok and inactivated vaccines have been compared, rates of the adverse and systemic reactions were similar,” Dr. Grohskopf said.
A motion was made to change the wording of the recommendation; however, the motion was not passed, and the eventual vote on the approval was conducted.
The ACIP also voted unanimously to change the safe age limit noted in influenza guidelines for use of Afluria (IIV3) from 9 years and older to 5 years and older. A footnote saying that the ACIP recommends Afluria for children 9 years and older will be removed.
This change, which mirrors the licensing Afluria has with the FDA, was based on research conducted by Seqirus that showed fever levels were the same for Afluria trivalent and quadrivalent vaccines in children 5 to 9 years old, both of which were less than historical vaccine rates.
The approved recommendations will be sent to the director of the CDC and the U.S. Department of Health and Human Services. Once reviewed and approved, the final recommendations will be published in the CDC’s Morbidity and Mortality Weekly Report. The committee members had no relevant financial disclosures.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
FROM AN ACIP MEETING
by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) after a lengthy debate over specifics regarding recommendations for pregnant women.
The proposed recommendation that sparked the debate would change the wording of the previous recommendation for pregnant women to receive a seasonal inactivated vaccine (IIV) to “any licensed, recommended, and age-appropriate, trivalent or quadrivalent IIV or RIV [recombinant influenza vaccine] may be used.”
“I think there’s a subtle, but important difference here between making what would appear to be an affirmative statement that RIV is safe in pregnant women, versus just staying silent on it, and saying ‘we’re not saying you shouldn’t use it, but we don’t have enough data to affirmatively say it is safe,’ ” said Cindy Pellegrini, senior vice president of Public Policy and Government Affairs at the March of Dimes Foundation.
In response, members of the committee pointed out that the responsibility of determining safety lies with the Food and Drug Administration, which has already licensed the Flublok trivalent vaccine with expectations that the quadrivalent vaccine soon will follow.
While Lisa Grohskopf, MD, MPH, medical officer of the influenza division of the CDC, did acknowledge that there were more data on the safety of inactivated influenza vaccines, she asserted to the committee that “the general overall safety profile of Flublok in comparison to inactivated vaccines is reassuring.”
“For example, one concern that arises is reactogenicity and inflammation. [In terms of] overall reactogenicity in the studies where Flublok and inactivated vaccines have been compared, rates of the adverse and systemic reactions were similar,” Dr. Grohskopf said.
A motion was made to change the wording of the recommendation; however, the motion was not passed, and the eventual vote on the approval was conducted.
The ACIP also voted unanimously to change the safe age limit noted in influenza guidelines for use of Afluria (IIV3) from 9 years and older to 5 years and older. A footnote saying that the ACIP recommends Afluria for children 9 years and older will be removed.
This change, which mirrors the licensing Afluria has with the FDA, was based on research conducted by Seqirus that showed fever levels were the same for Afluria trivalent and quadrivalent vaccines in children 5 to 9 years old, both of which were less than historical vaccine rates.
The approved recommendations will be sent to the director of the CDC and the U.S. Department of Health and Human Services. Once reviewed and approved, the final recommendations will be published in the CDC’s Morbidity and Mortality Weekly Report. The committee members had no relevant financial disclosures.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
FDA approves rituximab + hyaluronidase human for FL, DLBCL, and CLL
The Food and Drug Administration has approved rituximab plus hyaluronidase human for adult patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and chronic lymphocytic leukemia (CLL).
The combination product, to be marketed as Rituxan Hycela, is administered subcutaneously, shortening administration time to 5 to 7 minutes as compared with the several hours needed for intravenous infusion, the FDA said in a statement.
Approval was based on noninferior rituximab trough concentrations for the subcutaneously administered combination, compared with intravenous rituximab, and comparable efficacy and safety results as shown in multiple randomized clinical trials.
The most common adverse events seen with the combination in patients with FL included infections, neutropenia, nausea, constipation, cough, and fatigue. In patients with DLBCL, the most common adverse events were infections, neutropenia, alopecia, nausea, and anemia; in CLL patients, infections, neutropenia, nausea, thrombocytopenia, pyrexia, vomiting, and injection site erythema occurred most commonly.
The combination is indicated for the following previously approved indications for rituximab:
- Relapsed or refractory FL as a single agent.
- Previously untreated FL in combination with first line chemotherapy and, in patients achieving a complete or partial response to rituximab in combination with chemotherapy, as single-agent maintenance therapy.
- Nonprogressing (including stable disease) FL as a single agent after first-line cyclophosphamide, vincristine, and prednisone chemotherapy.
- Previously untreated DLBCL in combination with cyclophosphamide, doxorubicin, vincristine, prednisone or other anthracycline-based chemotherapy regimens.
- Previously untreated and previously treated CLL in combination with fludarabine and cyclophosphamide.
The recommended doses are 1,400 mg rituximab and 23,400 units hyaluronidase human for FL and DLBCL and 1,600 mg rituximab and 26,800 units hyaluronidase human for CLL. The combination treatment should be initiated only after patients have received at least one full dose of a rituximab product by intravenous infusion, according to the prescribing information.
Rituxan Hycela is marketed by Genentech.
The Food and Drug Administration has approved rituximab plus hyaluronidase human for adult patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and chronic lymphocytic leukemia (CLL).
The combination product, to be marketed as Rituxan Hycela, is administered subcutaneously, shortening administration time to 5 to 7 minutes as compared with the several hours needed for intravenous infusion, the FDA said in a statement.
Approval was based on noninferior rituximab trough concentrations for the subcutaneously administered combination, compared with intravenous rituximab, and comparable efficacy and safety results as shown in multiple randomized clinical trials.
The most common adverse events seen with the combination in patients with FL included infections, neutropenia, nausea, constipation, cough, and fatigue. In patients with DLBCL, the most common adverse events were infections, neutropenia, alopecia, nausea, and anemia; in CLL patients, infections, neutropenia, nausea, thrombocytopenia, pyrexia, vomiting, and injection site erythema occurred most commonly.
The combination is indicated for the following previously approved indications for rituximab:
- Relapsed or refractory FL as a single agent.
- Previously untreated FL in combination with first line chemotherapy and, in patients achieving a complete or partial response to rituximab in combination with chemotherapy, as single-agent maintenance therapy.
- Nonprogressing (including stable disease) FL as a single agent after first-line cyclophosphamide, vincristine, and prednisone chemotherapy.
- Previously untreated DLBCL in combination with cyclophosphamide, doxorubicin, vincristine, prednisone or other anthracycline-based chemotherapy regimens.
- Previously untreated and previously treated CLL in combination with fludarabine and cyclophosphamide.
The recommended doses are 1,400 mg rituximab and 23,400 units hyaluronidase human for FL and DLBCL and 1,600 mg rituximab and 26,800 units hyaluronidase human for CLL. The combination treatment should be initiated only after patients have received at least one full dose of a rituximab product by intravenous infusion, according to the prescribing information.
Rituxan Hycela is marketed by Genentech.
The Food and Drug Administration has approved rituximab plus hyaluronidase human for adult patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and chronic lymphocytic leukemia (CLL).
The combination product, to be marketed as Rituxan Hycela, is administered subcutaneously, shortening administration time to 5 to 7 minutes as compared with the several hours needed for intravenous infusion, the FDA said in a statement.
Approval was based on noninferior rituximab trough concentrations for the subcutaneously administered combination, compared with intravenous rituximab, and comparable efficacy and safety results as shown in multiple randomized clinical trials.
The most common adverse events seen with the combination in patients with FL included infections, neutropenia, nausea, constipation, cough, and fatigue. In patients with DLBCL, the most common adverse events were infections, neutropenia, alopecia, nausea, and anemia; in CLL patients, infections, neutropenia, nausea, thrombocytopenia, pyrexia, vomiting, and injection site erythema occurred most commonly.
The combination is indicated for the following previously approved indications for rituximab:
- Relapsed or refractory FL as a single agent.
- Previously untreated FL in combination with first line chemotherapy and, in patients achieving a complete or partial response to rituximab in combination with chemotherapy, as single-agent maintenance therapy.
- Nonprogressing (including stable disease) FL as a single agent after first-line cyclophosphamide, vincristine, and prednisone chemotherapy.
- Previously untreated DLBCL in combination with cyclophosphamide, doxorubicin, vincristine, prednisone or other anthracycline-based chemotherapy regimens.
- Previously untreated and previously treated CLL in combination with fludarabine and cyclophosphamide.
The recommended doses are 1,400 mg rituximab and 23,400 units hyaluronidase human for FL and DLBCL and 1,600 mg rituximab and 26,800 units hyaluronidase human for CLL. The combination treatment should be initiated only after patients have received at least one full dose of a rituximab product by intravenous infusion, according to the prescribing information.
Rituxan Hycela is marketed by Genentech.
Bendamustine plus rituximab may have edge for treating indolent NHL, MCL
CHICAGO – Overall survival was comparable at 5 years of follow up for three regimens in treatment-naive patients with indolent non-Hodgkin lymphoma (NHL) or mantle cell lymphoma (MCL), based on long-term results from the BRIGHT study.
While progression-free survival, event-free survival, and duration of response were significantly better with bendamustine plus rituximab (BR), overall survival at 5 years did not significantly differ in patients given this regimen and compared to patients given rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or rituximab with cyclophosphamide, vincristine and prednisone (R-CVP), Ian Flinn, MD, of Tennessee Oncology, Nashville, reported at the annual meeting of the American Society of Clinical Oncology.
Quality of life was somewhat better for the patients given BR, but those patients were also at higher risk for secondary malignancies (42 vs. 24), most of which were squamous cell carcinomas, observed Dr. Kahl, professor of medicine at Washington University, St. Louis.
In BRIGHT, 224 treatment-naive patients with indolent NHL or MCL were randomized to receive BR and were compared to 223 similar patients who received either R-CHOP (104 patients) or R-CVP (119 patients). At least six cycles of therapy were completed by 203 patients in the BR group and by 196 in the R-CHOP/R-CVP group. Rituximab maintenance therapy was given to 43% of the BR group and to 45% of the R-CHOP/R-CVP group.
For BR and R-CHOP/R-CVP, the 5-year progression-free survival rate was 65.5% (95% CI, 58.5-71.6) and 55.8% (95% CI, 48.4-62.5), respectively. The overall survival rate for the entire patient group was 81.7% (75.7-86.3) and 85% (79.3-89.3) respectively. Comparing BR and R-CHOP/R-CVP, the hazard ratio (95% CI) for progression-free survival was 0.61 (0.45-0.85; P = .0025), the HR for event-free survival was 0.63 (0.46-0.84; P = .0020), the HR for duration of response was 0.66 (0.47-0.92; P = .0134), and the HR for overall survival was 1.15 (0.72-1.84; P = .5461).
Similar results were found in indolent NHL (progression-free survival 0.70 [0.49-1.01; P = .0582]) and MCL (progression-free survival 0.40 [0.21-0.75; P = .0035]), with the strongest effect in MCL, Dr. Flinn said.
Dr. Kahl noted that the advantages for the BR regimen include that it is not associated with alopecia, neuropathy, or steroid issues, and that it may extend progression-free survival and time to next treatment. On the other hand, R-CHOP is associated with less GI toxicity, rash, opportunistic infections, and prolonged cytopenia. Also, the BR regimen was associated with a higher risk of secondary cancers, primarily squamous cell carcinomas.
There were 42 secondary malignancies in the BR group and 24 in the R-CHOP/R-CVP group, Dr. Flinn reported.
It is theoretically possible that BR equals R-CHOP plus maintenance therapy from an efficacy perspective, Dr. Kahl said.
As virtually all excess adverse event fatalities occurred during maintenance therapy, it is possible that maintenance therapy after BR “does more harm than good.” This high priority issue “should be evaluated in the BRIGHT data set,” Dr. Kahl recommended.
Teva Branded Pharmaceutical Products R&D sponsored the study. Dr. Flinn had no relationships to disclose; two of his fellow researchers are Teva employees. Dr. Kahl disclosed serving as an adviser or consultant to Abbvie, Acerta Pharma, Celgene, Cell Therapeutics, Genentech/Roche, Incyte, Infinity Pharmaceuticals, Juno Therapeutics, Millennium, Pharmacyclics, Sandoz, and Seattle Genetics.
mdales@frontlinemedcom.com
On Twitter @maryjodales
CHICAGO – Overall survival was comparable at 5 years of follow up for three regimens in treatment-naive patients with indolent non-Hodgkin lymphoma (NHL) or mantle cell lymphoma (MCL), based on long-term results from the BRIGHT study.
While progression-free survival, event-free survival, and duration of response were significantly better with bendamustine plus rituximab (BR), overall survival at 5 years did not significantly differ in patients given this regimen and compared to patients given rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or rituximab with cyclophosphamide, vincristine and prednisone (R-CVP), Ian Flinn, MD, of Tennessee Oncology, Nashville, reported at the annual meeting of the American Society of Clinical Oncology.
Quality of life was somewhat better for the patients given BR, but those patients were also at higher risk for secondary malignancies (42 vs. 24), most of which were squamous cell carcinomas, observed Dr. Kahl, professor of medicine at Washington University, St. Louis.
In BRIGHT, 224 treatment-naive patients with indolent NHL or MCL were randomized to receive BR and were compared to 223 similar patients who received either R-CHOP (104 patients) or R-CVP (119 patients). At least six cycles of therapy were completed by 203 patients in the BR group and by 196 in the R-CHOP/R-CVP group. Rituximab maintenance therapy was given to 43% of the BR group and to 45% of the R-CHOP/R-CVP group.
For BR and R-CHOP/R-CVP, the 5-year progression-free survival rate was 65.5% (95% CI, 58.5-71.6) and 55.8% (95% CI, 48.4-62.5), respectively. The overall survival rate for the entire patient group was 81.7% (75.7-86.3) and 85% (79.3-89.3) respectively. Comparing BR and R-CHOP/R-CVP, the hazard ratio (95% CI) for progression-free survival was 0.61 (0.45-0.85; P = .0025), the HR for event-free survival was 0.63 (0.46-0.84; P = .0020), the HR for duration of response was 0.66 (0.47-0.92; P = .0134), and the HR for overall survival was 1.15 (0.72-1.84; P = .5461).
Similar results were found in indolent NHL (progression-free survival 0.70 [0.49-1.01; P = .0582]) and MCL (progression-free survival 0.40 [0.21-0.75; P = .0035]), with the strongest effect in MCL, Dr. Flinn said.
Dr. Kahl noted that the advantages for the BR regimen include that it is not associated with alopecia, neuropathy, or steroid issues, and that it may extend progression-free survival and time to next treatment. On the other hand, R-CHOP is associated with less GI toxicity, rash, opportunistic infections, and prolonged cytopenia. Also, the BR regimen was associated with a higher risk of secondary cancers, primarily squamous cell carcinomas.
There were 42 secondary malignancies in the BR group and 24 in the R-CHOP/R-CVP group, Dr. Flinn reported.
It is theoretically possible that BR equals R-CHOP plus maintenance therapy from an efficacy perspective, Dr. Kahl said.
As virtually all excess adverse event fatalities occurred during maintenance therapy, it is possible that maintenance therapy after BR “does more harm than good.” This high priority issue “should be evaluated in the BRIGHT data set,” Dr. Kahl recommended.
Teva Branded Pharmaceutical Products R&D sponsored the study. Dr. Flinn had no relationships to disclose; two of his fellow researchers are Teva employees. Dr. Kahl disclosed serving as an adviser or consultant to Abbvie, Acerta Pharma, Celgene, Cell Therapeutics, Genentech/Roche, Incyte, Infinity Pharmaceuticals, Juno Therapeutics, Millennium, Pharmacyclics, Sandoz, and Seattle Genetics.
mdales@frontlinemedcom.com
On Twitter @maryjodales
CHICAGO – Overall survival was comparable at 5 years of follow up for three regimens in treatment-naive patients with indolent non-Hodgkin lymphoma (NHL) or mantle cell lymphoma (MCL), based on long-term results from the BRIGHT study.
While progression-free survival, event-free survival, and duration of response were significantly better with bendamustine plus rituximab (BR), overall survival at 5 years did not significantly differ in patients given this regimen and compared to patients given rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or rituximab with cyclophosphamide, vincristine and prednisone (R-CVP), Ian Flinn, MD, of Tennessee Oncology, Nashville, reported at the annual meeting of the American Society of Clinical Oncology.
Quality of life was somewhat better for the patients given BR, but those patients were also at higher risk for secondary malignancies (42 vs. 24), most of which were squamous cell carcinomas, observed Dr. Kahl, professor of medicine at Washington University, St. Louis.
In BRIGHT, 224 treatment-naive patients with indolent NHL or MCL were randomized to receive BR and were compared to 223 similar patients who received either R-CHOP (104 patients) or R-CVP (119 patients). At least six cycles of therapy were completed by 203 patients in the BR group and by 196 in the R-CHOP/R-CVP group. Rituximab maintenance therapy was given to 43% of the BR group and to 45% of the R-CHOP/R-CVP group.
For BR and R-CHOP/R-CVP, the 5-year progression-free survival rate was 65.5% (95% CI, 58.5-71.6) and 55.8% (95% CI, 48.4-62.5), respectively. The overall survival rate for the entire patient group was 81.7% (75.7-86.3) and 85% (79.3-89.3) respectively. Comparing BR and R-CHOP/R-CVP, the hazard ratio (95% CI) for progression-free survival was 0.61 (0.45-0.85; P = .0025), the HR for event-free survival was 0.63 (0.46-0.84; P = .0020), the HR for duration of response was 0.66 (0.47-0.92; P = .0134), and the HR for overall survival was 1.15 (0.72-1.84; P = .5461).
Similar results were found in indolent NHL (progression-free survival 0.70 [0.49-1.01; P = .0582]) and MCL (progression-free survival 0.40 [0.21-0.75; P = .0035]), with the strongest effect in MCL, Dr. Flinn said.
Dr. Kahl noted that the advantages for the BR regimen include that it is not associated with alopecia, neuropathy, or steroid issues, and that it may extend progression-free survival and time to next treatment. On the other hand, R-CHOP is associated with less GI toxicity, rash, opportunistic infections, and prolonged cytopenia. Also, the BR regimen was associated with a higher risk of secondary cancers, primarily squamous cell carcinomas.
There were 42 secondary malignancies in the BR group and 24 in the R-CHOP/R-CVP group, Dr. Flinn reported.
It is theoretically possible that BR equals R-CHOP plus maintenance therapy from an efficacy perspective, Dr. Kahl said.
As virtually all excess adverse event fatalities occurred during maintenance therapy, it is possible that maintenance therapy after BR “does more harm than good.” This high priority issue “should be evaluated in the BRIGHT data set,” Dr. Kahl recommended.
Teva Branded Pharmaceutical Products R&D sponsored the study. Dr. Flinn had no relationships to disclose; two of his fellow researchers are Teva employees. Dr. Kahl disclosed serving as an adviser or consultant to Abbvie, Acerta Pharma, Celgene, Cell Therapeutics, Genentech/Roche, Incyte, Infinity Pharmaceuticals, Juno Therapeutics, Millennium, Pharmacyclics, Sandoz, and Seattle Genetics.
mdales@frontlinemedcom.com
On Twitter @maryjodales
AT ASCO 2017
Key clinical point:
Major finding: For BR and R-CHOP/R-CVP, the 5-year progression-free survival rate was 65.5% (95% CI, 58.5-71.6) and 55.8% (95% CI, 48.4-62.5), respectively.
Data source: In BRIGHT, 224 treatment-naive patients with indolent non-Hodgkin lymphoma or mantle cell lymphoma were randomized to receive BR and were compared to 223 similar patients who received either R-CHOP (104 patients) or R-CVP (119 patients).
Disclosures: Teva Branded Pharmaceutical Products R&D sponsored the study. Dr. Flinn had no relationships to disclose; two of his fellow researchers are Teva employees. Dr. Kahl disclosed serving as an adviser or consultant to Abbvie, Acerta Pharma, Celgene, Cell Therapeutics, Genentech/Roche, Incyte, Infinity Pharmaceuticals, Juno Therapeutics, Millennium, Pharmacyclics, Sandoz, and Seattle Genetics.
Lenalidomide-rituximab induces high CR rate in untreated follicular lymphoma
LUGANO, SWITZERLAND – The chemotherapy-free combination of lenalidomide (Revlimid) and rituximab was highly active as frontline therapy for patients with low- and intermediate-risk follicular lymphoma in a multicenter phase II trial.
Among 66 patients with previously untreated follicular lymphoma, the overall response rate to the combination was 95%, including complete responses in 72% of patients. The 5-year progression-free survival (PFS) rate was 70%, reported John P. Leonard, MD, of Weill Cornell Medicine, New York.
“I think this overall is a useful validation – confirmation of the single-center data that showed that this [combination] in a multicenter setting can be a highly effective and reasonably well-tolerated treatment approach for patients with untreated follicular lymphoma,” he said at the International Conference on Malignant Lymphoma, on behalf of colleagues in the National Cancer Institute Alliance for Clinical Trials in Oncology and Cancer and Leukemia Group B (CALGB) 50803 trial.
In the 50803 study, the investigators enrolled 66 treatment-naive patients. The median age was 53 years (range 32-79). Patients were eligible if they had grade 1-3a, stage 3-4 or bulky stage 2 untreated follicular lymphoma, with Follicular Lymphoma International Prognostic Index (FLIPI) scores of 0-2.
They received lenalidomide 20 mg/day on days 1 through 21 of each 28-day cycle for 12 cycles, plus rituximab administered once weekly for each week of cycle 1, and on the first day of cycles 4, 6, 8 and 10.
The investigators also evaluated polymorphisms in the Fc fragment of immunoglobulin G receptor IIa and IIIa (FcGR2A/FcGR3A).
One of the 66 patients never started treatment, leaving 65 for the response analysis.
As noted, the overall response rate was 95%, including 94% of 21 patients with FLIPI 0 or 1 disease, and 96% of 44 patients with FLIPI 2 or 3. There were no associations between FLIPI score and likelihood of achieving a complete response, and no associations between FcR polymorphism or change in angiogenic markers and either complete responses or PFS, Dr. Leonard said.
Complete responses, the primary endpoint, were seen in 15 of the 21 (71%) of patients with FLIPI 0-1, and in 32 of the 44 (73%) with FLIPI 2-3, for an overall complete response rate of 72%.
Partial responses occurred in 5 patients (23%) with FLIPI 0-1 and 10 patients (23%) with FLIPI 2-3, for an overall PR rate of 23%.
Respective rates of stable disease were 0, 2%, and 2%. One patient in each FLIPI group was not evaluated because of adverse events.
After a median follow-up of 5 years, the progression free survival rate was 70%.
The most common grade 3 or 4 adverse events were neutropenia, seen in 21% of patients, and infections, seen in 40% (including one grade 3 febrile neutropenia).
Grade 1-2 fatigue was reported by 51 patients, and grade 3 fatigue was reported by 4.
Other grade 3 or 4 events seen in more than 5% of patients included rash in 9%, and hyperglycemia, hypophosphatemia, or hypertension, each in 6% of patients.
Celgene and Genentech supported the study. Dr. Leonard has served as an adviser/consultant to Celgene and other companies.
LUGANO, SWITZERLAND – The chemotherapy-free combination of lenalidomide (Revlimid) and rituximab was highly active as frontline therapy for patients with low- and intermediate-risk follicular lymphoma in a multicenter phase II trial.
Among 66 patients with previously untreated follicular lymphoma, the overall response rate to the combination was 95%, including complete responses in 72% of patients. The 5-year progression-free survival (PFS) rate was 70%, reported John P. Leonard, MD, of Weill Cornell Medicine, New York.
“I think this overall is a useful validation – confirmation of the single-center data that showed that this [combination] in a multicenter setting can be a highly effective and reasonably well-tolerated treatment approach for patients with untreated follicular lymphoma,” he said at the International Conference on Malignant Lymphoma, on behalf of colleagues in the National Cancer Institute Alliance for Clinical Trials in Oncology and Cancer and Leukemia Group B (CALGB) 50803 trial.
In the 50803 study, the investigators enrolled 66 treatment-naive patients. The median age was 53 years (range 32-79). Patients were eligible if they had grade 1-3a, stage 3-4 or bulky stage 2 untreated follicular lymphoma, with Follicular Lymphoma International Prognostic Index (FLIPI) scores of 0-2.
They received lenalidomide 20 mg/day on days 1 through 21 of each 28-day cycle for 12 cycles, plus rituximab administered once weekly for each week of cycle 1, and on the first day of cycles 4, 6, 8 and 10.
The investigators also evaluated polymorphisms in the Fc fragment of immunoglobulin G receptor IIa and IIIa (FcGR2A/FcGR3A).
One of the 66 patients never started treatment, leaving 65 for the response analysis.
As noted, the overall response rate was 95%, including 94% of 21 patients with FLIPI 0 or 1 disease, and 96% of 44 patients with FLIPI 2 or 3. There were no associations between FLIPI score and likelihood of achieving a complete response, and no associations between FcR polymorphism or change in angiogenic markers and either complete responses or PFS, Dr. Leonard said.
Complete responses, the primary endpoint, were seen in 15 of the 21 (71%) of patients with FLIPI 0-1, and in 32 of the 44 (73%) with FLIPI 2-3, for an overall complete response rate of 72%.
Partial responses occurred in 5 patients (23%) with FLIPI 0-1 and 10 patients (23%) with FLIPI 2-3, for an overall PR rate of 23%.
Respective rates of stable disease were 0, 2%, and 2%. One patient in each FLIPI group was not evaluated because of adverse events.
After a median follow-up of 5 years, the progression free survival rate was 70%.
The most common grade 3 or 4 adverse events were neutropenia, seen in 21% of patients, and infections, seen in 40% (including one grade 3 febrile neutropenia).
Grade 1-2 fatigue was reported by 51 patients, and grade 3 fatigue was reported by 4.
Other grade 3 or 4 events seen in more than 5% of patients included rash in 9%, and hyperglycemia, hypophosphatemia, or hypertension, each in 6% of patients.
Celgene and Genentech supported the study. Dr. Leonard has served as an adviser/consultant to Celgene and other companies.
LUGANO, SWITZERLAND – The chemotherapy-free combination of lenalidomide (Revlimid) and rituximab was highly active as frontline therapy for patients with low- and intermediate-risk follicular lymphoma in a multicenter phase II trial.
Among 66 patients with previously untreated follicular lymphoma, the overall response rate to the combination was 95%, including complete responses in 72% of patients. The 5-year progression-free survival (PFS) rate was 70%, reported John P. Leonard, MD, of Weill Cornell Medicine, New York.
“I think this overall is a useful validation – confirmation of the single-center data that showed that this [combination] in a multicenter setting can be a highly effective and reasonably well-tolerated treatment approach for patients with untreated follicular lymphoma,” he said at the International Conference on Malignant Lymphoma, on behalf of colleagues in the National Cancer Institute Alliance for Clinical Trials in Oncology and Cancer and Leukemia Group B (CALGB) 50803 trial.
In the 50803 study, the investigators enrolled 66 treatment-naive patients. The median age was 53 years (range 32-79). Patients were eligible if they had grade 1-3a, stage 3-4 or bulky stage 2 untreated follicular lymphoma, with Follicular Lymphoma International Prognostic Index (FLIPI) scores of 0-2.
They received lenalidomide 20 mg/day on days 1 through 21 of each 28-day cycle for 12 cycles, plus rituximab administered once weekly for each week of cycle 1, and on the first day of cycles 4, 6, 8 and 10.
The investigators also evaluated polymorphisms in the Fc fragment of immunoglobulin G receptor IIa and IIIa (FcGR2A/FcGR3A).
One of the 66 patients never started treatment, leaving 65 for the response analysis.
As noted, the overall response rate was 95%, including 94% of 21 patients with FLIPI 0 or 1 disease, and 96% of 44 patients with FLIPI 2 or 3. There were no associations between FLIPI score and likelihood of achieving a complete response, and no associations between FcR polymorphism or change in angiogenic markers and either complete responses or PFS, Dr. Leonard said.
Complete responses, the primary endpoint, were seen in 15 of the 21 (71%) of patients with FLIPI 0-1, and in 32 of the 44 (73%) with FLIPI 2-3, for an overall complete response rate of 72%.
Partial responses occurred in 5 patients (23%) with FLIPI 0-1 and 10 patients (23%) with FLIPI 2-3, for an overall PR rate of 23%.
Respective rates of stable disease were 0, 2%, and 2%. One patient in each FLIPI group was not evaluated because of adverse events.
After a median follow-up of 5 years, the progression free survival rate was 70%.
The most common grade 3 or 4 adverse events were neutropenia, seen in 21% of patients, and infections, seen in 40% (including one grade 3 febrile neutropenia).
Grade 1-2 fatigue was reported by 51 patients, and grade 3 fatigue was reported by 4.
Other grade 3 or 4 events seen in more than 5% of patients included rash in 9%, and hyperglycemia, hypophosphatemia, or hypertension, each in 6% of patients.
Celgene and Genentech supported the study. Dr. Leonard has served as an adviser/consultant to Celgene and other companies.
AT 14-ICML
Key clinical point: The combination of lenalidomide and rituximab was highly active against previously untreated follicular lymphoma.
Major finding: The overall response rate was 95%; 5-year progression-free survival was 70%.
Data source: Open-label prospective study of lenalidomide-rituximab in 66 patients with previously untreated follicular lymphoma.
Disclosures: Celgene and Genentech supported the study. Dr. Leonard has served as an adviser/consultant to Celgene and other companies.
Telemedicine Boosts Number of Native Americans Who Can Obtain Retina Exams
American Indians and Alaska Natives (AI/ANs) have a high risk of diabetes-related vision loss, in part because only half get the annual eye exam needed for timely diagnosis and treatment. But using an innovative telemedicine program, IHS increased the number of AI/ANs who receive an annual retina exam by 20% from 2007 to 2015.
The IHS teleophthalmology program, established in 2000, provides high-quality retinal exams in primary care clinics. More than 70,000 retinal exams have been done for AI/AN patients, IHS says. The exam can be done during a regular office visit without dilation. The retinal photographs are sent electronically to a central reading center where they’re interpreted by trained and certified IHS eye doctors.
The program, available at about 100 sites in 25 states, has not only increased access, IHS says, but also reduced the overall cost of care by preventing complications resulting from delayed or missed care. Screening and treating eye disease in patients with diabetes mellitus costs $3,190 per quality-adjusted life-year saved, IHS says; $840,000 would be saved annually in detecting high-risk diabetic retinopathy (DR). Another $1,090,000 would be saved by reducing the need for additional surgery for complications resulting from delayed identification of patients with high-risk DR.
The program has been validated to American Telemedicine Association Category 3, meaning its clinical outcome is equal to or better than a conventional eye examination for DR. As one of the few and largest programs validated and operating at this level, IHS says the teleophthalmology program has brought high-quality point-of-care specialty service to more than 150,000 AI/AN patients.
American Indians and Alaska Natives (AI/ANs) have a high risk of diabetes-related vision loss, in part because only half get the annual eye exam needed for timely diagnosis and treatment. But using an innovative telemedicine program, IHS increased the number of AI/ANs who receive an annual retina exam by 20% from 2007 to 2015.
The IHS teleophthalmology program, established in 2000, provides high-quality retinal exams in primary care clinics. More than 70,000 retinal exams have been done for AI/AN patients, IHS says. The exam can be done during a regular office visit without dilation. The retinal photographs are sent electronically to a central reading center where they’re interpreted by trained and certified IHS eye doctors.
The program, available at about 100 sites in 25 states, has not only increased access, IHS says, but also reduced the overall cost of care by preventing complications resulting from delayed or missed care. Screening and treating eye disease in patients with diabetes mellitus costs $3,190 per quality-adjusted life-year saved, IHS says; $840,000 would be saved annually in detecting high-risk diabetic retinopathy (DR). Another $1,090,000 would be saved by reducing the need for additional surgery for complications resulting from delayed identification of patients with high-risk DR.
The program has been validated to American Telemedicine Association Category 3, meaning its clinical outcome is equal to or better than a conventional eye examination for DR. As one of the few and largest programs validated and operating at this level, IHS says the teleophthalmology program has brought high-quality point-of-care specialty service to more than 150,000 AI/AN patients.
American Indians and Alaska Natives (AI/ANs) have a high risk of diabetes-related vision loss, in part because only half get the annual eye exam needed for timely diagnosis and treatment. But using an innovative telemedicine program, IHS increased the number of AI/ANs who receive an annual retina exam by 20% from 2007 to 2015.
The IHS teleophthalmology program, established in 2000, provides high-quality retinal exams in primary care clinics. More than 70,000 retinal exams have been done for AI/AN patients, IHS says. The exam can be done during a regular office visit without dilation. The retinal photographs are sent electronically to a central reading center where they’re interpreted by trained and certified IHS eye doctors.
The program, available at about 100 sites in 25 states, has not only increased access, IHS says, but also reduced the overall cost of care by preventing complications resulting from delayed or missed care. Screening and treating eye disease in patients with diabetes mellitus costs $3,190 per quality-adjusted life-year saved, IHS says; $840,000 would be saved annually in detecting high-risk diabetic retinopathy (DR). Another $1,090,000 would be saved by reducing the need for additional surgery for complications resulting from delayed identification of patients with high-risk DR.
The program has been validated to American Telemedicine Association Category 3, meaning its clinical outcome is equal to or better than a conventional eye examination for DR. As one of the few and largest programs validated and operating at this level, IHS says the teleophthalmology program has brought high-quality point-of-care specialty service to more than 150,000 AI/AN patients.
Tipoffs that an infant hospitalized with pertussis may require ICU
MADRID – Infants hospitalized for pertussis are more likely to develop severe disease requiring pediatric ICU admission if they are experiencing apnea, are unvaccinated against pertussis, or are less than 2 months old, Maria Arranz, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
“The presence of these parameters on admission should warn us of possible severe disease,” said Dr. Arranz of Gregorio Maranon Hospital in Madrid.
Dr. Arranz presented a retrospective observational study of 101 children under 1 year of age who were hospitalized for pertussis at the Madrid tertiary center prior to the hospital’s 2016 shift to a strategy of maternal immunization during pregnancy as a means of preventing pertussis in infancy. Thirteen percent of the children required admission to the pediatric ICU and thus by definition had severe disease.
Half of infants in the study were not vaccinated against pertussis. That proved to be a powerful risk factor for severe disease requiring an ICU stay. Only 8% of children with severe pertussis were vaccinated, compared with a 58% vaccination rate among those who avoided the ICU.
Apneic pauses were noted in 67% of the severe disease group, compared with 28% of the infants who didn’t need the ICU.
The pertussis patients admitted to the pediatric ICU averaged 1 month of age, compared with age 2 months in the nonsevere group.
The maximum leukocyte, lymphocyte, and neutrophil counts during the hospital stay of the severe disease group averaged 23,600 cells/mm3, 18,000/mm3, and 5,000/mm3, respectively, significantly greater than the 15,300, 10,700, and 3,900 cells/mm3 in infants who did not require the ICU. Levels of all three cells also were higher at admission in the severe pertussis group than in those who didn’t make it to the ICU, albeit not statistically significantly so.
Dr. Arranz reported having no financial conflicts of interest regarding her study.
MADRID – Infants hospitalized for pertussis are more likely to develop severe disease requiring pediatric ICU admission if they are experiencing apnea, are unvaccinated against pertussis, or are less than 2 months old, Maria Arranz, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
“The presence of these parameters on admission should warn us of possible severe disease,” said Dr. Arranz of Gregorio Maranon Hospital in Madrid.
Dr. Arranz presented a retrospective observational study of 101 children under 1 year of age who were hospitalized for pertussis at the Madrid tertiary center prior to the hospital’s 2016 shift to a strategy of maternal immunization during pregnancy as a means of preventing pertussis in infancy. Thirteen percent of the children required admission to the pediatric ICU and thus by definition had severe disease.
Half of infants in the study were not vaccinated against pertussis. That proved to be a powerful risk factor for severe disease requiring an ICU stay. Only 8% of children with severe pertussis were vaccinated, compared with a 58% vaccination rate among those who avoided the ICU.
Apneic pauses were noted in 67% of the severe disease group, compared with 28% of the infants who didn’t need the ICU.
The pertussis patients admitted to the pediatric ICU averaged 1 month of age, compared with age 2 months in the nonsevere group.
The maximum leukocyte, lymphocyte, and neutrophil counts during the hospital stay of the severe disease group averaged 23,600 cells/mm3, 18,000/mm3, and 5,000/mm3, respectively, significantly greater than the 15,300, 10,700, and 3,900 cells/mm3 in infants who did not require the ICU. Levels of all three cells also were higher at admission in the severe pertussis group than in those who didn’t make it to the ICU, albeit not statistically significantly so.
Dr. Arranz reported having no financial conflicts of interest regarding her study.
MADRID – Infants hospitalized for pertussis are more likely to develop severe disease requiring pediatric ICU admission if they are experiencing apnea, are unvaccinated against pertussis, or are less than 2 months old, Maria Arranz, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
“The presence of these parameters on admission should warn us of possible severe disease,” said Dr. Arranz of Gregorio Maranon Hospital in Madrid.
Dr. Arranz presented a retrospective observational study of 101 children under 1 year of age who were hospitalized for pertussis at the Madrid tertiary center prior to the hospital’s 2016 shift to a strategy of maternal immunization during pregnancy as a means of preventing pertussis in infancy. Thirteen percent of the children required admission to the pediatric ICU and thus by definition had severe disease.
Half of infants in the study were not vaccinated against pertussis. That proved to be a powerful risk factor for severe disease requiring an ICU stay. Only 8% of children with severe pertussis were vaccinated, compared with a 58% vaccination rate among those who avoided the ICU.
Apneic pauses were noted in 67% of the severe disease group, compared with 28% of the infants who didn’t need the ICU.
The pertussis patients admitted to the pediatric ICU averaged 1 month of age, compared with age 2 months in the nonsevere group.
The maximum leukocyte, lymphocyte, and neutrophil counts during the hospital stay of the severe disease group averaged 23,600 cells/mm3, 18,000/mm3, and 5,000/mm3, respectively, significantly greater than the 15,300, 10,700, and 3,900 cells/mm3 in infants who did not require the ICU. Levels of all three cells also were higher at admission in the severe pertussis group than in those who didn’t make it to the ICU, albeit not statistically significantly so.
Dr. Arranz reported having no financial conflicts of interest regarding her study.
AT ESPID 2017
Key clinical point:
Major finding: Among infants hospitalized for pertussis, apneic pauses were present in two-thirds of those with severe disease, ultimately resulting in admission to the pediatric ICU, compared with 28% of those who didn’t require an ICU stay.
Data source: This retrospective observational study sought to identify factors associated with severe pertussis requiring an ICU stay in a group of 101 Spanish infants hospitalized with the disease.
Disclosures: The presenter reported having no financial conflicts of interest regarding her study.
GALEN safe and effective in relapsed and refractory follicular lymphoma
LUGANO, SWITZERLAND – For patients with relapsed or refractory follicular lymphoma, a pairing of lenalidomide (Revlimid) and obinutuzumab (Gazyva) appeared to be especially useful among patients who had disease progression within 24 months, based on results from a Lymphoma Academic Research Organisation trial.
Among 86 patients who were enrolled in a phase II trial and were assessable for efficacy, overall response rates (ORR) with the combination therapy, nicknamed “GALEN,” were 80.2% by 1999 International Working Group criteria, and 74.4% according to the 2007 IWG criteria, reported Franck Morschhauser, MD, PhD, of the University of Lille, France.
The rationale for this combination is the known synergy between lenalidomide and rituximab in relapsed refractory non-Hodgkin lymphomas and in the frontline setting for patients with follicular lymphoma. Obinutuzumab, a follow-on to rituximab, is a unique type II glycoengineered monoclonal antibody directed against CD20, but with increased antibody-dependent cell-mediated cytotoxicity and increased direct cytotoxicity, compared with rituximab, he explained.
In the phase Ib part of the study, researchers settled on a dose of obinutuzumab 1000 mg and lenalidomide 20 mg. Obinutuzumab was administered on days 8, 15 and 22 and lenalidomide on days 1 to 21 of each 28 day cycle. Patients were evaluated for response after three cycles and at the end of induction (after completion of 4 to 6 cycles).
The maintenance phase consisted of obinutuzumab on day 1 of every other cycle beginning with cycle 1, and lenalidomide on days 1 through 22 for cycles 7 through 18. From cycles 19 through 24, obinutuzumab was given alone on the first day of every 56-day cycle.
The overall response rate (ORR) at the end of induction according to the IWG 1999 criteria, the primary endpoint, was 80.2%, including 39.5% complete or unconfirmed complete responses.
When the same patients were assessed according to 2007 IWG criteria, the ORR rate was slightly lower, at 74.4%, but the complete or unconfirmed complete response rate was slightly higher, at 44.2%.
An analysis of responses by time to relapse showed that the ORR among 24 patients with disease progression within 24 months was 70.8%, including 33.3% complete or unconfirmed complete responses by the 1999 criteria, and 66.7% with 54.2% complete or unconfirmed complete responses by the 2007 criteria.
ORR among the 64 patients with disease progression after more than 24 months was 83.9% with 41.9% complete or unconfirmed complete responses by 1999 criteria, and 77.4% with 40.3% complete or unconfirmed complete responses by 2007 criteria. The differences between the groups with disease progression within 24 months and later relapse groups were not significant.
A subanalysis by refractory status, however, showed that the 63 nonrefractory patients fared significantly better, with 87.3% ORR and 41.3% complete or unconfirmed complete responses by 1999 criteria, and 81.0% with 49.2% complete or unconfirmed complete response rate by 2007 determinations, compared with respective rates among 23 refractory patients of 60.9%/34.8% complete or unconfirmed complete response rate and 56.5% with 30.4% complete or unconfirmed complete responses (P = .0212 by 1999 criteria, and P = .022 by 2007 criteria).
After a median follow-up of 18 months, 1-year progression-free survival (PFS) among all patients was 75.5%, and 1-year overall survival (OS) was 88.8%.
There were no significant differences in either progression-free survival or overall survival by time to relapse. Although there appeared to be a nonsignificant trend toward worse outcomes among patients with refractory vs. nonrefractory disease, there was a significantly lower 1-year overall survival rate among refractory patients, at 71.5% compared with 95% for nonrefractory patients (censored logrank P = .0098).
Dr. Morschhauser said that the combination had no unexpected toxicities. Hematologic toxicities of grade 3 or greater included neutropenia in 28.4%, thrombocytopenia in 11.4%, and anemia and lymphopenia in 3.4% each.
The most common nonhematologic toxicities of all grades included infections in 62.5% of patients (grade 3 or greater in 6.8%), and asthenia in 52.3% of patients (grade 3 or greater in 2.3%). The only other grade 3 or greater toxicities were peripheral neuropathy in 1.1%, and infusion related rash in 3.4%.
Additional follow-up will be need for evaluation of the full impact of maintenance on outcomes, he added.
The study was funded by Celgene and Roche. Dr. Morschhauser disclosed receiving honoraria from and serving on advisory boards for both companies.
LUGANO, SWITZERLAND – For patients with relapsed or refractory follicular lymphoma, a pairing of lenalidomide (Revlimid) and obinutuzumab (Gazyva) appeared to be especially useful among patients who had disease progression within 24 months, based on results from a Lymphoma Academic Research Organisation trial.
Among 86 patients who were enrolled in a phase II trial and were assessable for efficacy, overall response rates (ORR) with the combination therapy, nicknamed “GALEN,” were 80.2% by 1999 International Working Group criteria, and 74.4% according to the 2007 IWG criteria, reported Franck Morschhauser, MD, PhD, of the University of Lille, France.
The rationale for this combination is the known synergy between lenalidomide and rituximab in relapsed refractory non-Hodgkin lymphomas and in the frontline setting for patients with follicular lymphoma. Obinutuzumab, a follow-on to rituximab, is a unique type II glycoengineered monoclonal antibody directed against CD20, but with increased antibody-dependent cell-mediated cytotoxicity and increased direct cytotoxicity, compared with rituximab, he explained.
In the phase Ib part of the study, researchers settled on a dose of obinutuzumab 1000 mg and lenalidomide 20 mg. Obinutuzumab was administered on days 8, 15 and 22 and lenalidomide on days 1 to 21 of each 28 day cycle. Patients were evaluated for response after three cycles and at the end of induction (after completion of 4 to 6 cycles).
The maintenance phase consisted of obinutuzumab on day 1 of every other cycle beginning with cycle 1, and lenalidomide on days 1 through 22 for cycles 7 through 18. From cycles 19 through 24, obinutuzumab was given alone on the first day of every 56-day cycle.
The overall response rate (ORR) at the end of induction according to the IWG 1999 criteria, the primary endpoint, was 80.2%, including 39.5% complete or unconfirmed complete responses.
When the same patients were assessed according to 2007 IWG criteria, the ORR rate was slightly lower, at 74.4%, but the complete or unconfirmed complete response rate was slightly higher, at 44.2%.
An analysis of responses by time to relapse showed that the ORR among 24 patients with disease progression within 24 months was 70.8%, including 33.3% complete or unconfirmed complete responses by the 1999 criteria, and 66.7% with 54.2% complete or unconfirmed complete responses by the 2007 criteria.
ORR among the 64 patients with disease progression after more than 24 months was 83.9% with 41.9% complete or unconfirmed complete responses by 1999 criteria, and 77.4% with 40.3% complete or unconfirmed complete responses by 2007 criteria. The differences between the groups with disease progression within 24 months and later relapse groups were not significant.
A subanalysis by refractory status, however, showed that the 63 nonrefractory patients fared significantly better, with 87.3% ORR and 41.3% complete or unconfirmed complete responses by 1999 criteria, and 81.0% with 49.2% complete or unconfirmed complete response rate by 2007 determinations, compared with respective rates among 23 refractory patients of 60.9%/34.8% complete or unconfirmed complete response rate and 56.5% with 30.4% complete or unconfirmed complete responses (P = .0212 by 1999 criteria, and P = .022 by 2007 criteria).
After a median follow-up of 18 months, 1-year progression-free survival (PFS) among all patients was 75.5%, and 1-year overall survival (OS) was 88.8%.
There were no significant differences in either progression-free survival or overall survival by time to relapse. Although there appeared to be a nonsignificant trend toward worse outcomes among patients with refractory vs. nonrefractory disease, there was a significantly lower 1-year overall survival rate among refractory patients, at 71.5% compared with 95% for nonrefractory patients (censored logrank P = .0098).
Dr. Morschhauser said that the combination had no unexpected toxicities. Hematologic toxicities of grade 3 or greater included neutropenia in 28.4%, thrombocytopenia in 11.4%, and anemia and lymphopenia in 3.4% each.
The most common nonhematologic toxicities of all grades included infections in 62.5% of patients (grade 3 or greater in 6.8%), and asthenia in 52.3% of patients (grade 3 or greater in 2.3%). The only other grade 3 or greater toxicities were peripheral neuropathy in 1.1%, and infusion related rash in 3.4%.
Additional follow-up will be need for evaluation of the full impact of maintenance on outcomes, he added.
The study was funded by Celgene and Roche. Dr. Morschhauser disclosed receiving honoraria from and serving on advisory boards for both companies.
LUGANO, SWITZERLAND – For patients with relapsed or refractory follicular lymphoma, a pairing of lenalidomide (Revlimid) and obinutuzumab (Gazyva) appeared to be especially useful among patients who had disease progression within 24 months, based on results from a Lymphoma Academic Research Organisation trial.
Among 86 patients who were enrolled in a phase II trial and were assessable for efficacy, overall response rates (ORR) with the combination therapy, nicknamed “GALEN,” were 80.2% by 1999 International Working Group criteria, and 74.4% according to the 2007 IWG criteria, reported Franck Morschhauser, MD, PhD, of the University of Lille, France.
The rationale for this combination is the known synergy between lenalidomide and rituximab in relapsed refractory non-Hodgkin lymphomas and in the frontline setting for patients with follicular lymphoma. Obinutuzumab, a follow-on to rituximab, is a unique type II glycoengineered monoclonal antibody directed against CD20, but with increased antibody-dependent cell-mediated cytotoxicity and increased direct cytotoxicity, compared with rituximab, he explained.
In the phase Ib part of the study, researchers settled on a dose of obinutuzumab 1000 mg and lenalidomide 20 mg. Obinutuzumab was administered on days 8, 15 and 22 and lenalidomide on days 1 to 21 of each 28 day cycle. Patients were evaluated for response after three cycles and at the end of induction (after completion of 4 to 6 cycles).
The maintenance phase consisted of obinutuzumab on day 1 of every other cycle beginning with cycle 1, and lenalidomide on days 1 through 22 for cycles 7 through 18. From cycles 19 through 24, obinutuzumab was given alone on the first day of every 56-day cycle.
The overall response rate (ORR) at the end of induction according to the IWG 1999 criteria, the primary endpoint, was 80.2%, including 39.5% complete or unconfirmed complete responses.
When the same patients were assessed according to 2007 IWG criteria, the ORR rate was slightly lower, at 74.4%, but the complete or unconfirmed complete response rate was slightly higher, at 44.2%.
An analysis of responses by time to relapse showed that the ORR among 24 patients with disease progression within 24 months was 70.8%, including 33.3% complete or unconfirmed complete responses by the 1999 criteria, and 66.7% with 54.2% complete or unconfirmed complete responses by the 2007 criteria.
ORR among the 64 patients with disease progression after more than 24 months was 83.9% with 41.9% complete or unconfirmed complete responses by 1999 criteria, and 77.4% with 40.3% complete or unconfirmed complete responses by 2007 criteria. The differences between the groups with disease progression within 24 months and later relapse groups were not significant.
A subanalysis by refractory status, however, showed that the 63 nonrefractory patients fared significantly better, with 87.3% ORR and 41.3% complete or unconfirmed complete responses by 1999 criteria, and 81.0% with 49.2% complete or unconfirmed complete response rate by 2007 determinations, compared with respective rates among 23 refractory patients of 60.9%/34.8% complete or unconfirmed complete response rate and 56.5% with 30.4% complete or unconfirmed complete responses (P = .0212 by 1999 criteria, and P = .022 by 2007 criteria).
After a median follow-up of 18 months, 1-year progression-free survival (PFS) among all patients was 75.5%, and 1-year overall survival (OS) was 88.8%.
There were no significant differences in either progression-free survival or overall survival by time to relapse. Although there appeared to be a nonsignificant trend toward worse outcomes among patients with refractory vs. nonrefractory disease, there was a significantly lower 1-year overall survival rate among refractory patients, at 71.5% compared with 95% for nonrefractory patients (censored logrank P = .0098).
Dr. Morschhauser said that the combination had no unexpected toxicities. Hematologic toxicities of grade 3 or greater included neutropenia in 28.4%, thrombocytopenia in 11.4%, and anemia and lymphopenia in 3.4% each.
The most common nonhematologic toxicities of all grades included infections in 62.5% of patients (grade 3 or greater in 6.8%), and asthenia in 52.3% of patients (grade 3 or greater in 2.3%). The only other grade 3 or greater toxicities were peripheral neuropathy in 1.1%, and infusion related rash in 3.4%.
Additional follow-up will be need for evaluation of the full impact of maintenance on outcomes, he added.
The study was funded by Celgene and Roche. Dr. Morschhauser disclosed receiving honoraria from and serving on advisory boards for both companies.
AT 14-ICML
Key clinical point: A combination of lenalidomide and obinutuzumab was safe and effective in patients with relapsed/refractory follicular lymphoma.
Major finding: The overall response rate according to 1999 International Working Group criteria was 80.2%, including 39.5% CR/CRu.
Data source: Single-arm phase II study with 86 patients evaluable for efficacy and 88 evaluable for safety.
Disclosures: The study was funded by Celgene and Roche. Dr. Morschhauser disclosed receiving honoraria from and serving on advisory boards for both companies.
Len plus anti-CD19 Mab MOR208 active against advanced DLBCL
LUGANO, SWITZERLAND – Combining lenalidomide (Revlimid) with an anti-CD19 monoclonal antibody labeled MOR208 showed promising activity in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who were ineligible for stem cell transplant and had poor prognosis, early interim results from a clinical study indicate.
Among 34 patients evaluable for response, the preliminary objective response rate (ORR) was 56%, including complete responses in 32% of patients, reported Gilles Salles, MD, PhD, of the University of Lyon, France.
MOR208 is a humanized anti-CD19 monoclonal antibody with the Fc-antibody region enhanced to improve cytotoxicity. Its mechanisms of action include natural killer cell–mediated antibody-dependent cell-mediated cytotoxicity, antibody-dependent cellular phagocytosis, and direct cytotoxicity.
In a preclinical study, a combination of MOR208 and lenalidomide showed synergistic antileukemic and antilymphoma activity both in vivo and in vitro, Dr. Salles said.
In addition, both lenalidomide and MOR208 have shown significant activity against relapsed, refractory B-cell non-Hodgkin lymphomas.
In an ongoing phase II, open-label study, Dr. Salles and his colleagues are enrolling transplant-ineligible patients 18 years and older with relapsed/refractory DLBCL, Eastern Cooperative Oncology Group status 0-2, and adequate organ function who had disease progression after 1-3 prior lines of therapy.
Patients with primary refractory DLBCL, double-hit or triple-hit DLBCL (i.e., mutations in Myc, BCL2, and/or BCL6), other NHL histological subtypes, or central nervous system lymphoma involvement are excluded.
Patients receive MOR208 12 mg/kg intravenously on days 1, 8, 15, and 22 for cycles 1-3 and on days 1 and 15 of cycles 4-12. Lenalidomide 25 mg orally is delivered on days 1-21 of each cycle. Patients who have stable disease or better at the end of 12 cycles can be maintained on MOR208 at the same dose on days 1 and 15.
As of the data cutoff on March 6, 2017, 44 patients had been enrolled, and 34 were evaluable for response. The median patient age was 73 years (range, 47-82 years).
At the time of the data presentation, ORR, the primary endpoint, was 56%, consisting of 32% complete responses (11 patients), 24% partial responses (8), 12% stable disease (4), and 32% of patients who either had disease progression or had not yet had a postbaseline response assessment.
The median time to response was 1.8 months, with a median time to complete response of 3.4 months. Of 19 responders, 16 continue to have a response, including 10 of 11 patients with complete responses.
The most common grade 3 or 4 hematologic toxicities were neutropenia, anemia, and thrombocytopenia. Nonhematologic toxicities of any grade included rashes in 20% of patients, pyrexia in 16%, diarrhea in 16%, asthenia in 14%, and pneumonia, bronchitis, and nausea in 11% each.
There were no reported infusion-related reactions with the antibody. In all, 27% of patients required a lenalidomide dose reduction – to 20 mg/day in 20% of patients and to 15 mg/day in 7%.
Study accrual, follow-up of patients on therapy, investigations of cell origin, and subgroup analyses are ongoing.
MorphoSys is sponsoring the study. Dr. Salles has received honoraria from Amgen, BMS, Celgene, Gilead, Janssen, Roche/Genentech, and Servier and is an advisor/consultant to many of the same companies.
LUGANO, SWITZERLAND – Combining lenalidomide (Revlimid) with an anti-CD19 monoclonal antibody labeled MOR208 showed promising activity in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who were ineligible for stem cell transplant and had poor prognosis, early interim results from a clinical study indicate.
Among 34 patients evaluable for response, the preliminary objective response rate (ORR) was 56%, including complete responses in 32% of patients, reported Gilles Salles, MD, PhD, of the University of Lyon, France.
MOR208 is a humanized anti-CD19 monoclonal antibody with the Fc-antibody region enhanced to improve cytotoxicity. Its mechanisms of action include natural killer cell–mediated antibody-dependent cell-mediated cytotoxicity, antibody-dependent cellular phagocytosis, and direct cytotoxicity.
In a preclinical study, a combination of MOR208 and lenalidomide showed synergistic antileukemic and antilymphoma activity both in vivo and in vitro, Dr. Salles said.
In addition, both lenalidomide and MOR208 have shown significant activity against relapsed, refractory B-cell non-Hodgkin lymphomas.
In an ongoing phase II, open-label study, Dr. Salles and his colleagues are enrolling transplant-ineligible patients 18 years and older with relapsed/refractory DLBCL, Eastern Cooperative Oncology Group status 0-2, and adequate organ function who had disease progression after 1-3 prior lines of therapy.
Patients with primary refractory DLBCL, double-hit or triple-hit DLBCL (i.e., mutations in Myc, BCL2, and/or BCL6), other NHL histological subtypes, or central nervous system lymphoma involvement are excluded.
Patients receive MOR208 12 mg/kg intravenously on days 1, 8, 15, and 22 for cycles 1-3 and on days 1 and 15 of cycles 4-12. Lenalidomide 25 mg orally is delivered on days 1-21 of each cycle. Patients who have stable disease or better at the end of 12 cycles can be maintained on MOR208 at the same dose on days 1 and 15.
As of the data cutoff on March 6, 2017, 44 patients had been enrolled, and 34 were evaluable for response. The median patient age was 73 years (range, 47-82 years).
At the time of the data presentation, ORR, the primary endpoint, was 56%, consisting of 32% complete responses (11 patients), 24% partial responses (8), 12% stable disease (4), and 32% of patients who either had disease progression or had not yet had a postbaseline response assessment.
The median time to response was 1.8 months, with a median time to complete response of 3.4 months. Of 19 responders, 16 continue to have a response, including 10 of 11 patients with complete responses.
The most common grade 3 or 4 hematologic toxicities were neutropenia, anemia, and thrombocytopenia. Nonhematologic toxicities of any grade included rashes in 20% of patients, pyrexia in 16%, diarrhea in 16%, asthenia in 14%, and pneumonia, bronchitis, and nausea in 11% each.
There were no reported infusion-related reactions with the antibody. In all, 27% of patients required a lenalidomide dose reduction – to 20 mg/day in 20% of patients and to 15 mg/day in 7%.
Study accrual, follow-up of patients on therapy, investigations of cell origin, and subgroup analyses are ongoing.
MorphoSys is sponsoring the study. Dr. Salles has received honoraria from Amgen, BMS, Celgene, Gilead, Janssen, Roche/Genentech, and Servier and is an advisor/consultant to many of the same companies.
LUGANO, SWITZERLAND – Combining lenalidomide (Revlimid) with an anti-CD19 monoclonal antibody labeled MOR208 showed promising activity in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who were ineligible for stem cell transplant and had poor prognosis, early interim results from a clinical study indicate.
Among 34 patients evaluable for response, the preliminary objective response rate (ORR) was 56%, including complete responses in 32% of patients, reported Gilles Salles, MD, PhD, of the University of Lyon, France.
MOR208 is a humanized anti-CD19 monoclonal antibody with the Fc-antibody region enhanced to improve cytotoxicity. Its mechanisms of action include natural killer cell–mediated antibody-dependent cell-mediated cytotoxicity, antibody-dependent cellular phagocytosis, and direct cytotoxicity.
In a preclinical study, a combination of MOR208 and lenalidomide showed synergistic antileukemic and antilymphoma activity both in vivo and in vitro, Dr. Salles said.
In addition, both lenalidomide and MOR208 have shown significant activity against relapsed, refractory B-cell non-Hodgkin lymphomas.
In an ongoing phase II, open-label study, Dr. Salles and his colleagues are enrolling transplant-ineligible patients 18 years and older with relapsed/refractory DLBCL, Eastern Cooperative Oncology Group status 0-2, and adequate organ function who had disease progression after 1-3 prior lines of therapy.
Patients with primary refractory DLBCL, double-hit or triple-hit DLBCL (i.e., mutations in Myc, BCL2, and/or BCL6), other NHL histological subtypes, or central nervous system lymphoma involvement are excluded.
Patients receive MOR208 12 mg/kg intravenously on days 1, 8, 15, and 22 for cycles 1-3 and on days 1 and 15 of cycles 4-12. Lenalidomide 25 mg orally is delivered on days 1-21 of each cycle. Patients who have stable disease or better at the end of 12 cycles can be maintained on MOR208 at the same dose on days 1 and 15.
As of the data cutoff on March 6, 2017, 44 patients had been enrolled, and 34 were evaluable for response. The median patient age was 73 years (range, 47-82 years).
At the time of the data presentation, ORR, the primary endpoint, was 56%, consisting of 32% complete responses (11 patients), 24% partial responses (8), 12% stable disease (4), and 32% of patients who either had disease progression or had not yet had a postbaseline response assessment.
The median time to response was 1.8 months, with a median time to complete response of 3.4 months. Of 19 responders, 16 continue to have a response, including 10 of 11 patients with complete responses.
The most common grade 3 or 4 hematologic toxicities were neutropenia, anemia, and thrombocytopenia. Nonhematologic toxicities of any grade included rashes in 20% of patients, pyrexia in 16%, diarrhea in 16%, asthenia in 14%, and pneumonia, bronchitis, and nausea in 11% each.
There were no reported infusion-related reactions with the antibody. In all, 27% of patients required a lenalidomide dose reduction – to 20 mg/day in 20% of patients and to 15 mg/day in 7%.
Study accrual, follow-up of patients on therapy, investigations of cell origin, and subgroup analyses are ongoing.
MorphoSys is sponsoring the study. Dr. Salles has received honoraria from Amgen, BMS, Celgene, Gilead, Janssen, Roche/Genentech, and Servier and is an advisor/consultant to many of the same companies.
AT 14-ICML
Key clinical point: A combination of the anti-CD19 monoclonal antibody MOR208 and the immunomodulator lenalidomide has shown good activity against relapsed/refractory diffuse large B-cell lymphoma.
Major finding: The preliminary objective response rate was 56%, including 32% complete responses.
Data source: An ongoing open-label phase II study with 44 patients out of a planned 80 enrolled.
Disclosures: MorphoSys is sponsoring the study. Dr. Salles has received honoraria from Amgen, BMS, Celgene, Gilead, Janssen, Roche/Genentech, and Servier and is an advisor or consultant to many of the same companies.