B Cell Lymphoma

Mantle cell lymphoma

Researchers say they have found evidence to suggest that patients with mantle cell lymphoma (MCL) should be evaluated for TP53 mutation and complex karyotype (CK) simultaneously before treatment.

The team’s study showed that TP53 mutation and CK occurred independently, but patients with both characteristics had poor prognosis.

All patients with TP53 mutation and CK died within 1.2 years of diagnosis, whereas about 94% of patients with neither characteristic were still alive at 2 years.

The researchers also found that, by combining TP53 mutation and CK, patients could be stratified into three prognostic groups that had distinct outcomes, regardless of treatment.

Vít Procházka, MD, PhD, of Palacký University in Olomouc, Czech Republic, and his colleagues reported these findings in Clinical Lymphoma, Myeloma & Leukemia.

The study included 74 consecutive adults newly diagnosed with MCL from 2000 through 2014. Seventy-three patients were treated with a rituximab-containing regimen. One patient, who did not have TP53 mutation or CK, was under observation without therapy.

Altogether, 48 patients (64.9%) had biological material available to perform analyses for TP53 mutation and CK. Of those, 4 patients were found to have both TP53 mutation and CK, 12 had one of the two markers, and 32 had neither.

While all patients with both markers died within 1.2 years, 2-year overall survival was 50.0% for those with one marker and 93.8% for those with neither marker (P<0.001).

Progression-free survival analyses showed similar results. The 2-year progression-free survival rate was 41.7% for patients with one marker and 78% for patients with neither marker (P<0.001).

Multivariate analysis showed that both TP53 mutation and CK were predictors of inferior progression-free survival and overall survival, independent of age and scores on the MCL International Prognostic Index.

While larger studies are needed to confirm these results, the researchers suggested that novel treatment approaches might be warranted for patients in the highest risk subgroup.

“The patients harboring the negative prognostic markers [TP53 mutation] and CK might be indicated for a novel induction treatment strategy probably in combination with maintenance therapy different from rituximab,” the researchers said.

This study was supported by grants from the Czech Ministry of Health and Palacký University. The researchers reported having no conflicts of interest.

Mantle cell lymphoma

Researchers say they have found evidence to suggest that patients with mantle cell lymphoma (MCL) should be evaluated for TP53 mutation and complex karyotype (CK) simultaneously before treatment.

The team’s study showed that TP53 mutation and CK occurred independently, but patients with both characteristics had poor prognosis.

All patients with TP53 mutation and CK died within 1.2 years of diagnosis, whereas about 94% of patients with neither characteristic were still alive at 2 years.

The researchers also found that, by combining TP53 mutation and CK, patients could be stratified into three prognostic groups that had distinct outcomes, regardless of treatment.

Vít Procházka, MD, PhD, of Palacký University in Olomouc, Czech Republic, and his colleagues reported these findings in Clinical Lymphoma, Myeloma & Leukemia.

The study included 74 consecutive adults newly diagnosed with MCL from 2000 through 2014. Seventy-three patients were treated with a rituximab-containing regimen. One patient, who did not have TP53 mutation or CK, was under observation without therapy.

Altogether, 48 patients (64.9%) had biological material available to perform analyses for TP53 mutation and CK. Of those, 4 patients were found to have both TP53 mutation and CK, 12 had one of the two markers, and 32 had neither.

While all patients with both markers died within 1.2 years, 2-year overall survival was 50.0% for those with one marker and 93.8% for those with neither marker (P<0.001).

Progression-free survival analyses showed similar results. The 2-year progression-free survival rate was 41.7% for patients with one marker and 78% for patients with neither marker (P<0.001).

Multivariate analysis showed that both TP53 mutation and CK were predictors of inferior progression-free survival and overall survival, independent of age and scores on the MCL International Prognostic Index.

While larger studies are needed to confirm these results, the researchers suggested that novel treatment approaches might be warranted for patients in the highest risk subgroup.

“The patients harboring the negative prognostic markers [TP53 mutation] and CK might be indicated for a novel induction treatment strategy probably in combination with maintenance therapy different from rituximab,” the researchers said.

This study was supported by grants from the Czech Ministry of Health and Palacký University. The researchers reported having no conflicts of interest.

Mantle cell lymphoma

Researchers say they have found evidence to suggest that patients with mantle cell lymphoma (MCL) should be evaluated for TP53 mutation and complex karyotype (CK) simultaneously before treatment.

The team’s study showed that TP53 mutation and CK occurred independently, but patients with both characteristics had poor prognosis.

All patients with TP53 mutation and CK died within 1.2 years of diagnosis, whereas about 94% of patients with neither characteristic were still alive at 2 years.

The researchers also found that, by combining TP53 mutation and CK, patients could be stratified into three prognostic groups that had distinct outcomes, regardless of treatment.

Vít Procházka, MD, PhD, of Palacký University in Olomouc, Czech Republic, and his colleagues reported these findings in Clinical Lymphoma, Myeloma & Leukemia.

The study included 74 consecutive adults newly diagnosed with MCL from 2000 through 2014. Seventy-three patients were treated with a rituximab-containing regimen. One patient, who did not have TP53 mutation or CK, was under observation without therapy.

Altogether, 48 patients (64.9%) had biological material available to perform analyses for TP53 mutation and CK. Of those, 4 patients were found to have both TP53 mutation and CK, 12 had one of the two markers, and 32 had neither.

While all patients with both markers died within 1.2 years, 2-year overall survival was 50.0% for those with one marker and 93.8% for those with neither marker (P<0.001).

Progression-free survival analyses showed similar results. The 2-year progression-free survival rate was 41.7% for patients with one marker and 78% for patients with neither marker (P<0.001).

Multivariate analysis showed that both TP53 mutation and CK were predictors of inferior progression-free survival and overall survival, independent of age and scores on the MCL International Prognostic Index.

While larger studies are needed to confirm these results, the researchers suggested that novel treatment approaches might be warranted for patients in the highest risk subgroup.

“The patients harboring the negative prognostic markers [TP53 mutation] and CK might be indicated for a novel induction treatment strategy probably in combination with maintenance therapy different from rituximab,” the researchers said.

This study was supported by grants from the Czech Ministry of Health and Palacký University. The researchers reported having no conflicts of interest.

Photo from Novartis

The National Institute for Health and Care Excellence (NICE) has issued a draft guidance saying it cannot recommend tisagenlecleucel (Kymriah) as a treatment for adults with diffuse large B-cell lymphoma (DLBCL).

Tisagenlecleucel is a chimeric antigen receptor (CAR) T-cell therapy that was recently approved by the European Commission (EC) to treat adults with relapsed or refractory DLBCL who have received two or more lines of systemic therapy.

Tisagenlecleucel is also EC-approved to treat patients up to 25 years of age who have B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post-transplant, or in second or later relapse.

Earlier this month, the National Health Service (NHS) of England announced that tisagenlecleucel will be made available for these ALL patients through the Cancer Drugs Fund.

However, NICE’s new draft guidance, issued September 19, says tisagenlecleucel cannot be made available for adults with relapsed/refractory DLBCL who have received two or more lines of systemic therapy.

NICE noted that there is no standard treatment for this patient group, and salvage chemotherapy is the most common treatment option.

Although the latest results from the JULIET trial¹ suggest tisagenlecleucel can produce responses in patients with relapsed/refractory DLBCL, there are no data comparing tisagenlecleucel with salvage chemotherapy.

In addition, tisagenlecleucel cannot be considered a life-extending treatment at the end of life, according to NICE criteria.

Furthermore, NICE said all cost-effectiveness estimates for tisagenlecleucel are above the range NICE normally considers acceptable, and tisagenlecleucel does not meet criteria for inclusion in the Cancer Drugs Fund.

The list price for tisagenlecleucel is £282,000. However, Novartis, the company developing tisagenlecleucel, has a confidential commercial arrangement with the NHS that lowers the price of tisagenlecleucel for the ALL indication. This arrangement would apply if tisagenlecleucel were recommended for the DLBCL indication.

All of the aforementioned issues aside, NICE said it does recognize that tisagenlecleucel has significant clinical benefits, and the agency welcomes further discussions on the CAR T-cell therapy’s cost-effectiveness.

NICE will consider comments on its draft guidance for tisagenlecleucel, together with any new evidence, at its next meeting on October 23, 2018.

Last month, NICE expressed similar sentiments about another CAR T-cell therapy, axicabtagene ciloleucel (Yescarta).

Axicabtagene ciloleucel is EC-approved to treat patients with relapsed/refractory DLBCL or primary mediastinal B-cell lymphoma who have received two or more lines of systemic therapy.

However, NICE said it isn’t clear how much of a benefit axicabtagene ciloleucel may provide over salvage chemotherapy. Additionally, the cost of axicabtagene ciloleucel is too high for it to be considered a cost-effective use of NHS resources, and the therapy does not meet criteria for inclusion in the Cancer Drugs Fund.

1. Borchmann P et al. AN UPDATED ANALYSIS OF JULIET, A GLOBAL PIVOTAL PHASE 2 TRIAL OF TISAGENLECLEUCEL IN ADULT PATIENTS WITH RELAPSED OR REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL). EHA 2018. Abstract S799.

Photo from Novartis

The National Institute for Health and Care Excellence (NICE) has issued a draft guidance saying it cannot recommend tisagenlecleucel (Kymriah) as a treatment for adults with diffuse large B-cell lymphoma (DLBCL).

Tisagenlecleucel is a chimeric antigen receptor (CAR) T-cell therapy that was recently approved by the European Commission (EC) to treat adults with relapsed or refractory DLBCL who have received two or more lines of systemic therapy.

Tisagenlecleucel is also EC-approved to treat patients up to 25 years of age who have B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post-transplant, or in second or later relapse.

Earlier this month, the National Health Service (NHS) of England announced that tisagenlecleucel will be made available for these ALL patients through the Cancer Drugs Fund.

However, NICE’s new draft guidance, issued September 19, says tisagenlecleucel cannot be made available for adults with relapsed/refractory DLBCL who have received two or more lines of systemic therapy.

NICE noted that there is no standard treatment for this patient group, and salvage chemotherapy is the most common treatment option.

Although the latest results from the JULIET trial¹ suggest tisagenlecleucel can produce responses in patients with relapsed/refractory DLBCL, there are no data comparing tisagenlecleucel with salvage chemotherapy.

In addition, tisagenlecleucel cannot be considered a life-extending treatment at the end of life, according to NICE criteria.

Furthermore, NICE said all cost-effectiveness estimates for tisagenlecleucel are above the range NICE normally considers acceptable, and tisagenlecleucel does not meet criteria for inclusion in the Cancer Drugs Fund.

The list price for tisagenlecleucel is £282,000. However, Novartis, the company developing tisagenlecleucel, has a confidential commercial arrangement with the NHS that lowers the price of tisagenlecleucel for the ALL indication. This arrangement would apply if tisagenlecleucel were recommended for the DLBCL indication.

All of the aforementioned issues aside, NICE said it does recognize that tisagenlecleucel has significant clinical benefits, and the agency welcomes further discussions on the CAR T-cell therapy’s cost-effectiveness.

NICE will consider comments on its draft guidance for tisagenlecleucel, together with any new evidence, at its next meeting on October 23, 2018.

Last month, NICE expressed similar sentiments about another CAR T-cell therapy, axicabtagene ciloleucel (Yescarta).

Axicabtagene ciloleucel is EC-approved to treat patients with relapsed/refractory DLBCL or primary mediastinal B-cell lymphoma who have received two or more lines of systemic therapy.

However, NICE said it isn’t clear how much of a benefit axicabtagene ciloleucel may provide over salvage chemotherapy. Additionally, the cost of axicabtagene ciloleucel is too high for it to be considered a cost-effective use of NHS resources, and the therapy does not meet criteria for inclusion in the Cancer Drugs Fund.

1. Borchmann P et al. AN UPDATED ANALYSIS OF JULIET, A GLOBAL PIVOTAL PHASE 2 TRIAL OF TISAGENLECLEUCEL IN ADULT PATIENTS WITH RELAPSED OR REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL). EHA 2018. Abstract S799.

Photo from Novartis

The National Institute for Health and Care Excellence (NICE) has issued a draft guidance saying it cannot recommend tisagenlecleucel (Kymriah) as a treatment for adults with diffuse large B-cell lymphoma (DLBCL).

Tisagenlecleucel is a chimeric antigen receptor (CAR) T-cell therapy that was recently approved by the European Commission (EC) to treat adults with relapsed or refractory DLBCL who have received two or more lines of systemic therapy.

Tisagenlecleucel is also EC-approved to treat patients up to 25 years of age who have B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post-transplant, or in second or later relapse.

Earlier this month, the National Health Service (NHS) of England announced that tisagenlecleucel will be made available for these ALL patients through the Cancer Drugs Fund.

However, NICE’s new draft guidance, issued September 19, says tisagenlecleucel cannot be made available for adults with relapsed/refractory DLBCL who have received two or more lines of systemic therapy.

NICE noted that there is no standard treatment for this patient group, and salvage chemotherapy is the most common treatment option.

Although the latest results from the JULIET trial¹ suggest tisagenlecleucel can produce responses in patients with relapsed/refractory DLBCL, there are no data comparing tisagenlecleucel with salvage chemotherapy.

In addition, tisagenlecleucel cannot be considered a life-extending treatment at the end of life, according to NICE criteria.

Furthermore, NICE said all cost-effectiveness estimates for tisagenlecleucel are above the range NICE normally considers acceptable, and tisagenlecleucel does not meet criteria for inclusion in the Cancer Drugs Fund.

The list price for tisagenlecleucel is £282,000. However, Novartis, the company developing tisagenlecleucel, has a confidential commercial arrangement with the NHS that lowers the price of tisagenlecleucel for the ALL indication. This arrangement would apply if tisagenlecleucel were recommended for the DLBCL indication.

All of the aforementioned issues aside, NICE said it does recognize that tisagenlecleucel has significant clinical benefits, and the agency welcomes further discussions on the CAR T-cell therapy’s cost-effectiveness.

NICE will consider comments on its draft guidance for tisagenlecleucel, together with any new evidence, at its next meeting on October 23, 2018.

Last month, NICE expressed similar sentiments about another CAR T-cell therapy, axicabtagene ciloleucel (Yescarta).

Axicabtagene ciloleucel is EC-approved to treat patients with relapsed/refractory DLBCL or primary mediastinal B-cell lymphoma who have received two or more lines of systemic therapy.

However, NICE said it isn’t clear how much of a benefit axicabtagene ciloleucel may provide over salvage chemotherapy. Additionally, the cost of axicabtagene ciloleucel is too high for it to be considered a cost-effective use of NHS resources, and the therapy does not meet criteria for inclusion in the Cancer Drugs Fund.

1. Borchmann P et al. AN UPDATED ANALYSIS OF JULIET, A GLOBAL PIVOTAL PHASE 2 TRIAL OF TISAGENLECLEUCEL IN ADULT PATIENTS WITH RELAPSED OR REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL). EHA 2018. Abstract S799.

The cost-effectiveness of tisagenlecleucel (Kymriah) depends on long-term clinical outcomes, which are presently unknown, according to investigators.

Courtesy Stanford University

If the long-term outcomes are more modest than clinical trials suggest, then payers may be unwilling to cover the costly therapy, reported John K. Lin, MD, of the Center for Primary Care and Outcomes Research at Stanford (Calif.) University, and his colleagues. Lowering the price or setting up an outcomes-based pricing structure may be necessary to get insurers to cover the therapy.

Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy that was approved by the Food and Drug Administration in August 2017 for relapsed or refractory pediatric B-cell acute lymphoblastic leukemia (ALL). In 2018, the FDA expanded the indication for tisagenlecleucel to include adults with relapsed or refractory large B-cell lymphoma, though outcomes from lymphoma trials are not analyzed in the current study.

At a wholesale acquisition cost of $475,000 per infusion, it is the most expensive existing oncology therapy to date, and can be accompanied by expensive, potentially fatal adverse effects. However, clinical trials suggest that tisagenlecleucel can offer years of relapse-free remission, thereby allowing patients to forgo other expensive therapies such as hematopoietic stem cell transplantation (HSCT).

“Although tisagenlecleucel-induced remission rates are promising, compared with those of established therapies (greater than 80% vs. less than 50%), only short-term follow-up data currently exist,” the investigators wrote in the Journal of Clinical Oncology. “Given the high cost and broad applicability in other malignancies of tisagenlecleucel, a pressing question for policy makers, payers, patients, and clinicians is whether the cost of therapy represents reasonable value.”

The study used a Markov model to assess various long-term clinical outcome rates and cost thresholds of tisagenlecleucel. The lifetime cost of therapy was assessed and compared with costs of existing therapies.

The results showed that a 5-year relapse free survival rate of 40% would make the present cost ($475,000) of tisagenlecleucel economically reasonable. In this scenario, the increased life expectancy would be 12.1 years and would result in an additional 5.07 quality-adjusted life years (QALY) gained at a cost of $61,000 per QALY, compared with blinatumomab.

But if long-term outcomes are less favorable, tisagenlecleucel becomes much less cost effective. A 5-year relapse-free survival rate of 20% would drop increased life expectancy to 3.8 years, resulting in 1.80 QALYs gained and raising the cost to $151,000 per QALY.

“Our results suggest that at tisagenlecleucel’s current price and payment structure, its economic value is uncertain,” the investigators wrote.

They suggested a price drop to $200,000 or $350,000, which would allow the drug to remain cost effective even in a worse-case scenario, in which patients relapse and tisagenlecleucel is a bridge to transplant. Another option is to move to outcomes-based pricing. Making payment conditional on 7 months of remission would make the treatment cost effective, according to the analysis.

“Price reductions of tisagenlecleucel or payment only for longer-term remissions would favorably influence cost-effectiveness, even if long-term clinical outcomes are modest,” the investigators wrote.

The study was funded by a Veterans Affairs Office of Academic Affiliations advanced fellowship in health service and research development, and a National Center for Advancing Translational Science Clinical and Translational Science Award. One of the study coauthors reported consulting and research funding from Novartis.

SOURCE: Lin et al. J Clin Oncol. 2018 Sep 13. doi: 10.1200/JCO.2018.79.0642.

The cost-effectiveness of tisagenlecleucel (Kymriah) depends on long-term clinical outcomes, which are presently unknown, according to investigators.

Courtesy Stanford University

If the long-term outcomes are more modest than clinical trials suggest, then payers may be unwilling to cover the costly therapy, reported John K. Lin, MD, of the Center for Primary Care and Outcomes Research at Stanford (Calif.) University, and his colleagues. Lowering the price or setting up an outcomes-based pricing structure may be necessary to get insurers to cover the therapy.

Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy that was approved by the Food and Drug Administration in August 2017 for relapsed or refractory pediatric B-cell acute lymphoblastic leukemia (ALL). In 2018, the FDA expanded the indication for tisagenlecleucel to include adults with relapsed or refractory large B-cell lymphoma, though outcomes from lymphoma trials are not analyzed in the current study.

At a wholesale acquisition cost of $475,000 per infusion, it is the most expensive existing oncology therapy to date, and can be accompanied by expensive, potentially fatal adverse effects. However, clinical trials suggest that tisagenlecleucel can offer years of relapse-free remission, thereby allowing patients to forgo other expensive therapies such as hematopoietic stem cell transplantation (HSCT).

“Although tisagenlecleucel-induced remission rates are promising, compared with those of established therapies (greater than 80% vs. less than 50%), only short-term follow-up data currently exist,” the investigators wrote in the Journal of Clinical Oncology. “Given the high cost and broad applicability in other malignancies of tisagenlecleucel, a pressing question for policy makers, payers, patients, and clinicians is whether the cost of therapy represents reasonable value.”

The study used a Markov model to assess various long-term clinical outcome rates and cost thresholds of tisagenlecleucel. The lifetime cost of therapy was assessed and compared with costs of existing therapies.

The results showed that a 5-year relapse free survival rate of 40% would make the present cost ($475,000) of tisagenlecleucel economically reasonable. In this scenario, the increased life expectancy would be 12.1 years and would result in an additional 5.07 quality-adjusted life years (QALY) gained at a cost of $61,000 per QALY, compared with blinatumomab.

But if long-term outcomes are less favorable, tisagenlecleucel becomes much less cost effective. A 5-year relapse-free survival rate of 20% would drop increased life expectancy to 3.8 years, resulting in 1.80 QALYs gained and raising the cost to $151,000 per QALY.

“Our results suggest that at tisagenlecleucel’s current price and payment structure, its economic value is uncertain,” the investigators wrote.

They suggested a price drop to $200,000 or $350,000, which would allow the drug to remain cost effective even in a worse-case scenario, in which patients relapse and tisagenlecleucel is a bridge to transplant. Another option is to move to outcomes-based pricing. Making payment conditional on 7 months of remission would make the treatment cost effective, according to the analysis.

“Price reductions of tisagenlecleucel or payment only for longer-term remissions would favorably influence cost-effectiveness, even if long-term clinical outcomes are modest,” the investigators wrote.

The study was funded by a Veterans Affairs Office of Academic Affiliations advanced fellowship in health service and research development, and a National Center for Advancing Translational Science Clinical and Translational Science Award. One of the study coauthors reported consulting and research funding from Novartis.

SOURCE: Lin et al. J Clin Oncol. 2018 Sep 13. doi: 10.1200/JCO.2018.79.0642.

The cost-effectiveness of tisagenlecleucel (Kymriah) depends on long-term clinical outcomes, which are presently unknown, according to investigators.

Courtesy Stanford University

If the long-term outcomes are more modest than clinical trials suggest, then payers may be unwilling to cover the costly therapy, reported John K. Lin, MD, of the Center for Primary Care and Outcomes Research at Stanford (Calif.) University, and his colleagues. Lowering the price or setting up an outcomes-based pricing structure may be necessary to get insurers to cover the therapy.

Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy that was approved by the Food and Drug Administration in August 2017 for relapsed or refractory pediatric B-cell acute lymphoblastic leukemia (ALL). In 2018, the FDA expanded the indication for tisagenlecleucel to include adults with relapsed or refractory large B-cell lymphoma, though outcomes from lymphoma trials are not analyzed in the current study.

At a wholesale acquisition cost of $475,000 per infusion, it is the most expensive existing oncology therapy to date, and can be accompanied by expensive, potentially fatal adverse effects. However, clinical trials suggest that tisagenlecleucel can offer years of relapse-free remission, thereby allowing patients to forgo other expensive therapies such as hematopoietic stem cell transplantation (HSCT).

“Although tisagenlecleucel-induced remission rates are promising, compared with those of established therapies (greater than 80% vs. less than 50%), only short-term follow-up data currently exist,” the investigators wrote in the Journal of Clinical Oncology. “Given the high cost and broad applicability in other malignancies of tisagenlecleucel, a pressing question for policy makers, payers, patients, and clinicians is whether the cost of therapy represents reasonable value.”

The study used a Markov model to assess various long-term clinical outcome rates and cost thresholds of tisagenlecleucel. The lifetime cost of therapy was assessed and compared with costs of existing therapies.

The results showed that a 5-year relapse free survival rate of 40% would make the present cost ($475,000) of tisagenlecleucel economically reasonable. In this scenario, the increased life expectancy would be 12.1 years and would result in an additional 5.07 quality-adjusted life years (QALY) gained at a cost of $61,000 per QALY, compared with blinatumomab.

But if long-term outcomes are less favorable, tisagenlecleucel becomes much less cost effective. A 5-year relapse-free survival rate of 20% would drop increased life expectancy to 3.8 years, resulting in 1.80 QALYs gained and raising the cost to $151,000 per QALY.

“Our results suggest that at tisagenlecleucel’s current price and payment structure, its economic value is uncertain,” the investigators wrote.

They suggested a price drop to $200,000 or $350,000, which would allow the drug to remain cost effective even in a worse-case scenario, in which patients relapse and tisagenlecleucel is a bridge to transplant. Another option is to move to outcomes-based pricing. Making payment conditional on 7 months of remission would make the treatment cost effective, according to the analysis.

“Price reductions of tisagenlecleucel or payment only for longer-term remissions would favorably influence cost-effectiveness, even if long-term clinical outcomes are modest,” the investigators wrote.

The study was funded by a Veterans Affairs Office of Academic Affiliations advanced fellowship in health service and research development, and a National Center for Advancing Translational Science Clinical and Translational Science Award. One of the study coauthors reported consulting and research funding from Novartis.

SOURCE: Lin et al. J Clin Oncol. 2018 Sep 13. doi: 10.1200/JCO.2018.79.0642.

A wide variety of hematologic, dermatologic, and solid organ malignancies are associated with pruritus, a large, single-center, retrospective study suggests.

Blacks with pruritus had a higher odds ratio of hematologic malignancies, among others, while whites had higher likelihood of liver, gastrointestinal, respiratory and gynecologic cancers, results of the study show.

Blacks with pruritus had higher ORs for hematologic and soft tissue malignancies including those of the muscle, fat, and peripheral nerve, investigators said, while whites had higher ORs for skin and liver malignancies.

The investigators also looked at the prevalence of skin eruptions in patients with pruritus and malignancy. “Eruption is variable by malignancy type and points to differing underlying mechanisms of pruritus,” they reported.

The highest rates of skin eruption were in patients with myeloid leukemia at 66%, followed by bone cancers at 58%, lymphocytic leukemia at 57%, multiple myeloma at 53%, and bronchus at 53%. The lowest rates of skin eruption were in patients with gallbladder and biliary tract, colon, pancreas, and liver malignancies.

Dr. Kwatra reported that he is an advisory board member for Menlo Therapeutics and Trevi Therapeutics.

SOURCE: Kwatra SG et al. J Am Acad Dermatol. 2018 Sep 11. doi: 10.1016/j.jaad.2018.08.044.

A wide variety of hematologic, dermatologic, and solid organ malignancies are associated with pruritus, a large, single-center, retrospective study suggests.

Blacks with pruritus had a higher odds ratio of hematologic malignancies, among others, while whites had higher likelihood of liver, gastrointestinal, respiratory and gynecologic cancers, results of the study show.

Blacks with pruritus had higher ORs for hematologic and soft tissue malignancies including those of the muscle, fat, and peripheral nerve, investigators said, while whites had higher ORs for skin and liver malignancies.

The investigators also looked at the prevalence of skin eruptions in patients with pruritus and malignancy. “Eruption is variable by malignancy type and points to differing underlying mechanisms of pruritus,” they reported.

The highest rates of skin eruption were in patients with myeloid leukemia at 66%, followed by bone cancers at 58%, lymphocytic leukemia at 57%, multiple myeloma at 53%, and bronchus at 53%. The lowest rates of skin eruption were in patients with gallbladder and biliary tract, colon, pancreas, and liver malignancies.

Dr. Kwatra reported that he is an advisory board member for Menlo Therapeutics and Trevi Therapeutics.

SOURCE: Kwatra SG et al. J Am Acad Dermatol. 2018 Sep 11. doi: 10.1016/j.jaad.2018.08.044.

A wide variety of hematologic, dermatologic, and solid organ malignancies are associated with pruritus, a large, single-center, retrospective study suggests.

Blacks with pruritus had a higher odds ratio of hematologic malignancies, among others, while whites had higher likelihood of liver, gastrointestinal, respiratory and gynecologic cancers, results of the study show.

Blacks with pruritus had higher ORs for hematologic and soft tissue malignancies including those of the muscle, fat, and peripheral nerve, investigators said, while whites had higher ORs for skin and liver malignancies.

The investigators also looked at the prevalence of skin eruptions in patients with pruritus and malignancy. “Eruption is variable by malignancy type and points to differing underlying mechanisms of pruritus,” they reported.

The highest rates of skin eruption were in patients with myeloid leukemia at 66%, followed by bone cancers at 58%, lymphocytic leukemia at 57%, multiple myeloma at 53%, and bronchus at 53%. The lowest rates of skin eruption were in patients with gallbladder and biliary tract, colon, pancreas, and liver malignancies.

Dr. Kwatra reported that he is an advisory board member for Menlo Therapeutics and Trevi Therapeutics.

SOURCE: Kwatra SG et al. J Am Acad Dermatol. 2018 Sep 11. doi: 10.1016/j.jaad.2018.08.044.

At least four new trials in mantle cell lymphoma (MCL) are preparing to launch, according to records posted on Clinicaltrials.gov.

The range of new studies are occurring around the world and examine the association of lenalidomide with tumor flare reaction, maintenance ixazomib for newly diagnosed patients, the addition of bortezomib to ibrutinib in ibrutinib-released patients, and acalabrutinib plus bendamustine and rituximab and cytarabine and rituximab in untreated patients.

Acalabrutinib With Alternating Cycles of Bendamustine/Rituximab and Cytarabine/Rituximab for Untreated Mantle Cell Lymphoma (NCT03623373) is slated to start on Oct. 31, 2018, and be completed in 2025.

The trial, which is not yet recruiting, is estimated to enroll 15 participants. The phase 1 study will be aimed at evaluating the efficacy and safety of acalabrutinib plus bendamustine and rituximab and cytarabine and rituximab in MCL patients who are treatment naive. The primary outcome measure is stem cell mobilization success rate in patients treated with this regimen. The phase 1 study is preparation for a larger cooperative group trial that aims to achieve a standard induction regimen for MCL in transplant-eligible patients.

The study is sponsored by Washington University, St. Louis, in collaboration with Acerta Pharma.

Ibrutinib-relapsed MCL

Bortezomib in Combination With Ibrutinib in Ibrutinib Relapsed Mantle Cell Lymphoma (NCT03617484) is scheduled to start in September 2018 and be completed in 2021. It is estimated to enroll 35 patients but is not yet recruiting.

The phase 2, open-label study is aimed at evaluating the efficacy of the ibrutinib/bortezomib in MCL patients who relapsed on ibrutinib alone. The primary outcome is the overall response rate at 6 months based on the Lugano criteria.

The trial is sponsored by the University of Michigan, Ann Arbor.

Ixazomib Maintenance in Patients With Newly Diagnosed Mantle Cell Lymphoma (NCT03616782) launched in August 2018 and is expected to be completed in 2022.

The phase 2 trial is expected to enroll 98 patients but has not started recruitment yet. In the open-label, multicenter study, newly diagnosed MCL patients will receive induction chemotherapy and those who achieve at least a partial response will be eligible to move on to the experimental phase – maintenance ixazomib. At least 8 weeks after completing induction, patients can receive ixazomib orally on days 1, 8, and 15 for 4 weeks. Treatment repeats every 4 weeks for up to 2 years unless the disease progresses or there is unacceptable toxicity. The primary outcome measure is 2-year progression-free survival.

The trial is sponsored by Ho Sup Lee, MD, of Kosin University Gospel Hospital in Busan, South Korea, in collaboration with Takeda.

PASS MCL-005

The Noninterventional Study in Patients With Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL) to Investigate the Association of Lenalidomide With Tumor Flare Reaction and High Tumor Burden, called PASS MCL-005 (NCT03647124) is slated to start at the end of September 2018 and wrap up in 2026.

The retrospective cohort study will rely on data collection from Nordic registries and national health databases. The researchers will analyze records from sites where lenalidomide treatment for relapsed/refractory MCL is reimbursed. The estimated enrollment is 560 participants.

The primary goal is to quantify and characterize the event of tumor flare reaction by tumor burden in relapsed/refractory MCL patients who were treated with lenalidomide in a real-world setting.

The European-based study is sponsored by Celgene.

[email protected]

At least four new trials in mantle cell lymphoma (MCL) are preparing to launch, according to records posted on Clinicaltrials.gov.

The range of new studies are occurring around the world and examine the association of lenalidomide with tumor flare reaction, maintenance ixazomib for newly diagnosed patients, the addition of bortezomib to ibrutinib in ibrutinib-released patients, and acalabrutinib plus bendamustine and rituximab and cytarabine and rituximab in untreated patients.

Acalabrutinib With Alternating Cycles of Bendamustine/Rituximab and Cytarabine/Rituximab for Untreated Mantle Cell Lymphoma (NCT03623373) is slated to start on Oct. 31, 2018, and be completed in 2025.

The trial, which is not yet recruiting, is estimated to enroll 15 participants. The phase 1 study will be aimed at evaluating the efficacy and safety of acalabrutinib plus bendamustine and rituximab and cytarabine and rituximab in MCL patients who are treatment naive. The primary outcome measure is stem cell mobilization success rate in patients treated with this regimen. The phase 1 study is preparation for a larger cooperative group trial that aims to achieve a standard induction regimen for MCL in transplant-eligible patients.

The study is sponsored by Washington University, St. Louis, in collaboration with Acerta Pharma.

Ibrutinib-relapsed MCL

Bortezomib in Combination With Ibrutinib in Ibrutinib Relapsed Mantle Cell Lymphoma (NCT03617484) is scheduled to start in September 2018 and be completed in 2021. It is estimated to enroll 35 patients but is not yet recruiting.

The phase 2, open-label study is aimed at evaluating the efficacy of the ibrutinib/bortezomib in MCL patients who relapsed on ibrutinib alone. The primary outcome is the overall response rate at 6 months based on the Lugano criteria.

The trial is sponsored by the University of Michigan, Ann Arbor.

Ixazomib Maintenance in Patients With Newly Diagnosed Mantle Cell Lymphoma (NCT03616782) launched in August 2018 and is expected to be completed in 2022.

The phase 2 trial is expected to enroll 98 patients but has not started recruitment yet. In the open-label, multicenter study, newly diagnosed MCL patients will receive induction chemotherapy and those who achieve at least a partial response will be eligible to move on to the experimental phase – maintenance ixazomib. At least 8 weeks after completing induction, patients can receive ixazomib orally on days 1, 8, and 15 for 4 weeks. Treatment repeats every 4 weeks for up to 2 years unless the disease progresses or there is unacceptable toxicity. The primary outcome measure is 2-year progression-free survival.

The trial is sponsored by Ho Sup Lee, MD, of Kosin University Gospel Hospital in Busan, South Korea, in collaboration with Takeda.

PASS MCL-005

The Noninterventional Study in Patients With Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL) to Investigate the Association of Lenalidomide With Tumor Flare Reaction and High Tumor Burden, called PASS MCL-005 (NCT03647124) is slated to start at the end of September 2018 and wrap up in 2026.

The retrospective cohort study will rely on data collection from Nordic registries and national health databases. The researchers will analyze records from sites where lenalidomide treatment for relapsed/refractory MCL is reimbursed. The estimated enrollment is 560 participants.

The primary goal is to quantify and characterize the event of tumor flare reaction by tumor burden in relapsed/refractory MCL patients who were treated with lenalidomide in a real-world setting.

The European-based study is sponsored by Celgene.

[email protected]

At least four new trials in mantle cell lymphoma (MCL) are preparing to launch, according to records posted on Clinicaltrials.gov.

The range of new studies are occurring around the world and examine the association of lenalidomide with tumor flare reaction, maintenance ixazomib for newly diagnosed patients, the addition of bortezomib to ibrutinib in ibrutinib-released patients, and acalabrutinib plus bendamustine and rituximab and cytarabine and rituximab in untreated patients.

Acalabrutinib With Alternating Cycles of Bendamustine/Rituximab and Cytarabine/Rituximab for Untreated Mantle Cell Lymphoma (NCT03623373) is slated to start on Oct. 31, 2018, and be completed in 2025.

The trial, which is not yet recruiting, is estimated to enroll 15 participants. The phase 1 study will be aimed at evaluating the efficacy and safety of acalabrutinib plus bendamustine and rituximab and cytarabine and rituximab in MCL patients who are treatment naive. The primary outcome measure is stem cell mobilization success rate in patients treated with this regimen. The phase 1 study is preparation for a larger cooperative group trial that aims to achieve a standard induction regimen for MCL in transplant-eligible patients.

The study is sponsored by Washington University, St. Louis, in collaboration with Acerta Pharma.

Ibrutinib-relapsed MCL

Bortezomib in Combination With Ibrutinib in Ibrutinib Relapsed Mantle Cell Lymphoma (NCT03617484) is scheduled to start in September 2018 and be completed in 2021. It is estimated to enroll 35 patients but is not yet recruiting.

The phase 2, open-label study is aimed at evaluating the efficacy of the ibrutinib/bortezomib in MCL patients who relapsed on ibrutinib alone. The primary outcome is the overall response rate at 6 months based on the Lugano criteria.

The trial is sponsored by the University of Michigan, Ann Arbor.

Ixazomib Maintenance in Patients With Newly Diagnosed Mantle Cell Lymphoma (NCT03616782) launched in August 2018 and is expected to be completed in 2022.

The phase 2 trial is expected to enroll 98 patients but has not started recruitment yet. In the open-label, multicenter study, newly diagnosed MCL patients will receive induction chemotherapy and those who achieve at least a partial response will be eligible to move on to the experimental phase – maintenance ixazomib. At least 8 weeks after completing induction, patients can receive ixazomib orally on days 1, 8, and 15 for 4 weeks. Treatment repeats every 4 weeks for up to 2 years unless the disease progresses or there is unacceptable toxicity. The primary outcome measure is 2-year progression-free survival.

The trial is sponsored by Ho Sup Lee, MD, of Kosin University Gospel Hospital in Busan, South Korea, in collaboration with Takeda.

PASS MCL-005

The Noninterventional Study in Patients With Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL) to Investigate the Association of Lenalidomide With Tumor Flare Reaction and High Tumor Burden, called PASS MCL-005 (NCT03647124) is slated to start at the end of September 2018 and wrap up in 2026.

The retrospective cohort study will rely on data collection from Nordic registries and national health databases. The researchers will analyze records from sites where lenalidomide treatment for relapsed/refractory MCL is reimbursed. The estimated enrollment is 560 participants.

The primary goal is to quantify and characterize the event of tumor flare reaction by tumor burden in relapsed/refractory MCL patients who were treated with lenalidomide in a real-world setting.

The European-based study is sponsored by Celgene.

[email protected]

The Food and Drug Administration has expanded the label for venetoclax tablets (Venclexta) to include data on minimal residual disease.

The drug’s prescribing information will now include details on minimal residual disease (MRD) negativity in previously treated patients with chronic lymphocytic leukemia (CLL) who received venetoclax in combination with rituximab in the phase 3 MURANO trial.

The combination of venetoclax and rituximab was approved by the FDA in June 2018 for the treatment of patients with CLL or small lymphocytic lymphoma, with or without 17p deletion, who received at least one prior therapy.

The MURANO trial (NCT02005471), which supported the FDA approval, included 389 patients with relapsed or refractory CLL. They were randomized to receive venetoclax plus rituximab or bendamustine plus rituximab (N Engl J Med. 2018; 378:1107-20).

Researchers evaluated MRD in patients who achieved a partial response or better. MRD was assessed using allele-specific oligonucleotide polymerase chain reaction; the definition of MRD negativity was less than one CLL cell per 10,000 lymphocytes.

The researchers assessed MRD in the peripheral blood after about 9 months on therapy (3 months after the last dose of rituximab). At that time, 53% (103/194) of patients in the venetoclax-rituximab arm were MRD negative, as were 12% (23/195) of patients in the bendamustine-rituximab arm.

The researchers also assessed MRD in the peripheral blood of patients with a complete response or complete response with incomplete marrow recovery. MRD negativity was achieved by 3% (6/194) of these patients in the venetoclax-rituximab arm and 2% (3/195) in the bendamustine-rituximab arm.

Venetoclax is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the United States and by AbbVie outside of the United States.

[email protected]

The Food and Drug Administration has expanded the label for venetoclax tablets (Venclexta) to include data on minimal residual disease.

The drug’s prescribing information will now include details on minimal residual disease (MRD) negativity in previously treated patients with chronic lymphocytic leukemia (CLL) who received venetoclax in combination with rituximab in the phase 3 MURANO trial.

The combination of venetoclax and rituximab was approved by the FDA in June 2018 for the treatment of patients with CLL or small lymphocytic lymphoma, with or without 17p deletion, who received at least one prior therapy.

The MURANO trial (NCT02005471), which supported the FDA approval, included 389 patients with relapsed or refractory CLL. They were randomized to receive venetoclax plus rituximab or bendamustine plus rituximab (N Engl J Med. 2018; 378:1107-20).

Researchers evaluated MRD in patients who achieved a partial response or better. MRD was assessed using allele-specific oligonucleotide polymerase chain reaction; the definition of MRD negativity was less than one CLL cell per 10,000 lymphocytes.

The researchers assessed MRD in the peripheral blood after about 9 months on therapy (3 months after the last dose of rituximab). At that time, 53% (103/194) of patients in the venetoclax-rituximab arm were MRD negative, as were 12% (23/195) of patients in the bendamustine-rituximab arm.

The researchers also assessed MRD in the peripheral blood of patients with a complete response or complete response with incomplete marrow recovery. MRD negativity was achieved by 3% (6/194) of these patients in the venetoclax-rituximab arm and 2% (3/195) in the bendamustine-rituximab arm.

Venetoclax is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the United States and by AbbVie outside of the United States.

[email protected]

The Food and Drug Administration has expanded the label for venetoclax tablets (Venclexta) to include data on minimal residual disease.

The drug’s prescribing information will now include details on minimal residual disease (MRD) negativity in previously treated patients with chronic lymphocytic leukemia (CLL) who received venetoclax in combination with rituximab in the phase 3 MURANO trial.

The combination of venetoclax and rituximab was approved by the FDA in June 2018 for the treatment of patients with CLL or small lymphocytic lymphoma, with or without 17p deletion, who received at least one prior therapy.

The MURANO trial (NCT02005471), which supported the FDA approval, included 389 patients with relapsed or refractory CLL. They were randomized to receive venetoclax plus rituximab or bendamustine plus rituximab (N Engl J Med. 2018; 378:1107-20).

Researchers evaluated MRD in patients who achieved a partial response or better. MRD was assessed using allele-specific oligonucleotide polymerase chain reaction; the definition of MRD negativity was less than one CLL cell per 10,000 lymphocytes.

The researchers assessed MRD in the peripheral blood after about 9 months on therapy (3 months after the last dose of rituximab). At that time, 53% (103/194) of patients in the venetoclax-rituximab arm were MRD negative, as were 12% (23/195) of patients in the bendamustine-rituximab arm.

The researchers also assessed MRD in the peripheral blood of patients with a complete response or complete response with incomplete marrow recovery. MRD negativity was achieved by 3% (6/194) of these patients in the venetoclax-rituximab arm and 2% (3/195) in the bendamustine-rituximab arm.

Venetoclax is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the United States and by AbbVie outside of the United States.

[email protected]

Photo courtesy of Abbvie

The U.S. Food and Drug Administration (FDA) has expanded the label for venetoclax tablets (Venclexta^®) to include data on minimal residual disease (MRD).

The drug’s prescribing information now includes details on MRD negativity in previously treated patients with chronic lymphocytic leukemia (CLL) who received venetoclax in combination with rituximab in the phase 3 MURANO trial.

The combination of venetoclax and rituximab was FDA approved in June for the treatment of patients with CLL or small lymphocytic lymphoma, with or without 17p deletion, who received at least one prior therapy.

The MURANO trial (NCT02005471), which supported the FDA approval, included 389 patients with relapsed or refractory CLL.

The patients were randomized to receive:

• Venetoclax at 400 mg daily for 24 months (after a 5-week ramp-up period) plus rituximab at 375 mg/m² on day 1 for the first cycle and at 500 mg/m²  on day 1 for cycles 2 to 6 (n=194)
• Bendamustine at 70 mg/m² on days 1 and 2 for 6 cycles plus rituximab at the same schedule as the venetoclax arm (n=195).

Researchers evaluated MRD in patients who achieved a partial response or better. MRD was assessed using allele-specific oligonucleotide polymerase chain reaction, and the definition of MRD negativity was less than one CLL cell per 10,000 lymphocytes.

The researchers assessed MRD in the peripheral blood 3 months after the last dose of rituximab. At that time, 53% (103/194) of patients in the venetoclax-rituximab arm were MRD negative, as were 12% (23/195) of patients in the bendamustine-rituximab arm.

The researchers also assessed MRD in the peripheral blood of patients with a complete response (CR) or CR with incomplete marrow recovery (CRi). MRD negativity was achieved by 3% (6/194) of these patients in the venetoclax-rituximab arm and 2% (3/195) in the bendamustine-rituximab arm.

Three percent (3/106) of patients in the venetoclax arm who achieved CR/CRi were MRD negative in both the peripheral blood and the bone marrow.

“The rates of MRD negativity seen with Venclexta plus rituximab are very encouraging,” said MURANO investigator John Seymour, MBBS, PhD, of the Peter MacCallum Cancer Centre in Melbourne, Victoria, Australia.

Additional results from the MURANO trial were published in The New England Journal of Medicine in March and are included in the prescribing information for venetoclax.

Venetoclax is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside the U.S.

Photo courtesy of Abbvie

The U.S. Food and Drug Administration (FDA) has expanded the label for venetoclax tablets (Venclexta^®) to include data on minimal residual disease (MRD).

The drug’s prescribing information now includes details on MRD negativity in previously treated patients with chronic lymphocytic leukemia (CLL) who received venetoclax in combination with rituximab in the phase 3 MURANO trial.

The combination of venetoclax and rituximab was FDA approved in June for the treatment of patients with CLL or small lymphocytic lymphoma, with or without 17p deletion, who received at least one prior therapy.

The MURANO trial (NCT02005471), which supported the FDA approval, included 389 patients with relapsed or refractory CLL.

The patients were randomized to receive:

• Venetoclax at 400 mg daily for 24 months (after a 5-week ramp-up period) plus rituximab at 375 mg/m² on day 1 for the first cycle and at 500 mg/m²  on day 1 for cycles 2 to 6 (n=194)
• Bendamustine at 70 mg/m² on days 1 and 2 for 6 cycles plus rituximab at the same schedule as the venetoclax arm (n=195).

Researchers evaluated MRD in patients who achieved a partial response or better. MRD was assessed using allele-specific oligonucleotide polymerase chain reaction, and the definition of MRD negativity was less than one CLL cell per 10,000 lymphocytes.

The researchers assessed MRD in the peripheral blood 3 months after the last dose of rituximab. At that time, 53% (103/194) of patients in the venetoclax-rituximab arm were MRD negative, as were 12% (23/195) of patients in the bendamustine-rituximab arm.

The researchers also assessed MRD in the peripheral blood of patients with a complete response (CR) or CR with incomplete marrow recovery (CRi). MRD negativity was achieved by 3% (6/194) of these patients in the venetoclax-rituximab arm and 2% (3/195) in the bendamustine-rituximab arm.

Three percent (3/106) of patients in the venetoclax arm who achieved CR/CRi were MRD negative in both the peripheral blood and the bone marrow.

“The rates of MRD negativity seen with Venclexta plus rituximab are very encouraging,” said MURANO investigator John Seymour, MBBS, PhD, of the Peter MacCallum Cancer Centre in Melbourne, Victoria, Australia.

Additional results from the MURANO trial were published in The New England Journal of Medicine in March and are included in the prescribing information for venetoclax.

Venetoclax is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside the U.S.

Photo courtesy of Abbvie

The U.S. Food and Drug Administration (FDA) has expanded the label for venetoclax tablets (Venclexta^®) to include data on minimal residual disease (MRD).

The drug’s prescribing information now includes details on MRD negativity in previously treated patients with chronic lymphocytic leukemia (CLL) who received venetoclax in combination with rituximab in the phase 3 MURANO trial.

The combination of venetoclax and rituximab was FDA approved in June for the treatment of patients with CLL or small lymphocytic lymphoma, with or without 17p deletion, who received at least one prior therapy.

The MURANO trial (NCT02005471), which supported the FDA approval, included 389 patients with relapsed or refractory CLL.

The patients were randomized to receive:

• Venetoclax at 400 mg daily for 24 months (after a 5-week ramp-up period) plus rituximab at 375 mg/m² on day 1 for the first cycle and at 500 mg/m²  on day 1 for cycles 2 to 6 (n=194)
• Bendamustine at 70 mg/m² on days 1 and 2 for 6 cycles plus rituximab at the same schedule as the venetoclax arm (n=195).

Researchers evaluated MRD in patients who achieved a partial response or better. MRD was assessed using allele-specific oligonucleotide polymerase chain reaction, and the definition of MRD negativity was less than one CLL cell per 10,000 lymphocytes.

The researchers assessed MRD in the peripheral blood 3 months after the last dose of rituximab. At that time, 53% (103/194) of patients in the venetoclax-rituximab arm were MRD negative, as were 12% (23/195) of patients in the bendamustine-rituximab arm.

The researchers also assessed MRD in the peripheral blood of patients with a complete response (CR) or CR with incomplete marrow recovery (CRi). MRD negativity was achieved by 3% (6/194) of these patients in the venetoclax-rituximab arm and 2% (3/195) in the bendamustine-rituximab arm.

Three percent (3/106) of patients in the venetoclax arm who achieved CR/CRi were MRD negative in both the peripheral blood and the bone marrow.

“The rates of MRD negativity seen with Venclexta plus rituximab are very encouraging,” said MURANO investigator John Seymour, MBBS, PhD, of the Peter MacCallum Cancer Centre in Melbourne, Victoria, Australia.

Additional results from the MURANO trial were published in The New England Journal of Medicine in March and are included in the prescribing information for venetoclax.

Venetoclax is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside the U.S.

Fluoroquinolones are recommended for adults with cancer-related immunosuppression if they are at high risk of infection, according to an updated clinical practice guideline on antimicrobial prophylaxis.

By contrast, patients with solid tumors are not routinely recommended to receive antibiotic prophylaxis, according to the guideline, developed by the American Society of Clinical Oncology (ASCO) with the Infectious Diseases Society of America (IDSA).

The guideline includes antibacterial, antifungal, and antiviral prophylaxis recommendations, along with additional precautions such as hand hygiene that may reduce infection risk.

Released in the Journal of Clinical Oncology, the updated guidelines were developed by an expert panel cochaired by Christopher R. Flowers, MD of Emory University, Atlanta, and Randy A. Taplitz, MD of the University of California, San Diego, Health.

For the most part, the panel endorsed the previous ASCO recommendations, published in 2013. However, the panel considered six new high-quality studies and six new or updated meta-analyses to make modifications and add some new recommendations.

Fluoroquinolones, in the 2013 guideline, were recommended over trimethoprim-sulfamethoxazole because of fewer adverse events leading to treatment discontinuation. Panelists for the new guidelines said they continued to support that recommendation, based on an updated literature review.

That review showed significant reductions in both febrile neutropenia incidence and all-cause mortality, not only for patients at high risk of febrile neutropenia or profound, protracted neutropenia but also for lower-risk patients with solid tumors, they said.

However, the benefits did not sufficiently outweigh the harms to justify recommending fluoroquinolone prophylaxis for all patients with solid tumors or lymphoma, according to the report from the expert panel.

Those harms could include antibiotic-associated adverse effects, emergence of resistance, and Clostridium difficile infections, they said.

Accordingly, they recommended fluoroquinolone prophylaxis for the high-risk patients, including most patients with acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) or those undergoing hematopoietic stem-cell transplantation (HSCT).

Similarly, the panel recommended that high-risk patients should receive antifungal prophylaxis with an oral triazole or parenteral echinocandin, while prophylaxis would not be routinely recommended for solid tumor patients.

By contrast, all patients undergoing chemotherapy for malignancy should receive yearly influenza vaccination with an inactivated quadrivalent vaccine, the panel said in its antiviral prophylaxis recommendations.

Family members, household contacts, and health care providers also should receive influenza vaccinations, said the panel, endorsing recommendations from the Centers for Disease Control and Prevention that were also cited in the 2013 ASCO guidelines.

Health care workers should follow hand hygiene and respiratory hygiene/cough etiquette to reduce risk of pathogen transmission, the panel said, endorsing CDC recommendations cited in the previous guideline.

However, the panel said they recommend against interventions such as neutropenic diet, footwear exchange, nutritional supplements, and surgical masks.

“Evidence of clinical benefit is lacking” for those interventions, they said.

Participants in the expert panel disclosed potential conflicts of interest related to Merck, Chimerix, GlyPharma Therapeutic, Pfizer, Cidara Therapeutics, Celgene, Astellas Pharma, Gilead Sciences, and Allergan, among other entities.
 

SOURCE: Taplitz RA et al. J Clin Oncol. 2018 Sept 4. doi: 10.1200/JCO.18.00374.

Fluoroquinolones are recommended for adults with cancer-related immunosuppression if they are at high risk of infection, according to an updated clinical practice guideline on antimicrobial prophylaxis.

By contrast, patients with solid tumors are not routinely recommended to receive antibiotic prophylaxis, according to the guideline, developed by the American Society of Clinical Oncology (ASCO) with the Infectious Diseases Society of America (IDSA).

The guideline includes antibacterial, antifungal, and antiviral prophylaxis recommendations, along with additional precautions such as hand hygiene that may reduce infection risk.

Released in the Journal of Clinical Oncology, the updated guidelines were developed by an expert panel cochaired by Christopher R. Flowers, MD of Emory University, Atlanta, and Randy A. Taplitz, MD of the University of California, San Diego, Health.

For the most part, the panel endorsed the previous ASCO recommendations, published in 2013. However, the panel considered six new high-quality studies and six new or updated meta-analyses to make modifications and add some new recommendations.

Fluoroquinolones, in the 2013 guideline, were recommended over trimethoprim-sulfamethoxazole because of fewer adverse events leading to treatment discontinuation. Panelists for the new guidelines said they continued to support that recommendation, based on an updated literature review.

That review showed significant reductions in both febrile neutropenia incidence and all-cause mortality, not only for patients at high risk of febrile neutropenia or profound, protracted neutropenia but also for lower-risk patients with solid tumors, they said.

However, the benefits did not sufficiently outweigh the harms to justify recommending fluoroquinolone prophylaxis for all patients with solid tumors or lymphoma, according to the report from the expert panel.

Those harms could include antibiotic-associated adverse effects, emergence of resistance, and Clostridium difficile infections, they said.

Accordingly, they recommended fluoroquinolone prophylaxis for the high-risk patients, including most patients with acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) or those undergoing hematopoietic stem-cell transplantation (HSCT).

Similarly, the panel recommended that high-risk patients should receive antifungal prophylaxis with an oral triazole or parenteral echinocandin, while prophylaxis would not be routinely recommended for solid tumor patients.

By contrast, all patients undergoing chemotherapy for malignancy should receive yearly influenza vaccination with an inactivated quadrivalent vaccine, the panel said in its antiviral prophylaxis recommendations.

Family members, household contacts, and health care providers also should receive influenza vaccinations, said the panel, endorsing recommendations from the Centers for Disease Control and Prevention that were also cited in the 2013 ASCO guidelines.

Health care workers should follow hand hygiene and respiratory hygiene/cough etiquette to reduce risk of pathogen transmission, the panel said, endorsing CDC recommendations cited in the previous guideline.

However, the panel said they recommend against interventions such as neutropenic diet, footwear exchange, nutritional supplements, and surgical masks.

“Evidence of clinical benefit is lacking” for those interventions, they said.

Participants in the expert panel disclosed potential conflicts of interest related to Merck, Chimerix, GlyPharma Therapeutic, Pfizer, Cidara Therapeutics, Celgene, Astellas Pharma, Gilead Sciences, and Allergan, among other entities.
 

SOURCE: Taplitz RA et al. J Clin Oncol. 2018 Sept 4. doi: 10.1200/JCO.18.00374.

Fluoroquinolones are recommended for adults with cancer-related immunosuppression if they are at high risk of infection, according to an updated clinical practice guideline on antimicrobial prophylaxis.

By contrast, patients with solid tumors are not routinely recommended to receive antibiotic prophylaxis, according to the guideline, developed by the American Society of Clinical Oncology (ASCO) with the Infectious Diseases Society of America (IDSA).

The guideline includes antibacterial, antifungal, and antiviral prophylaxis recommendations, along with additional precautions such as hand hygiene that may reduce infection risk.

Released in the Journal of Clinical Oncology, the updated guidelines were developed by an expert panel cochaired by Christopher R. Flowers, MD of Emory University, Atlanta, and Randy A. Taplitz, MD of the University of California, San Diego, Health.

For the most part, the panel endorsed the previous ASCO recommendations, published in 2013. However, the panel considered six new high-quality studies and six new or updated meta-analyses to make modifications and add some new recommendations.

Fluoroquinolones, in the 2013 guideline, were recommended over trimethoprim-sulfamethoxazole because of fewer adverse events leading to treatment discontinuation. Panelists for the new guidelines said they continued to support that recommendation, based on an updated literature review.

That review showed significant reductions in both febrile neutropenia incidence and all-cause mortality, not only for patients at high risk of febrile neutropenia or profound, protracted neutropenia but also for lower-risk patients with solid tumors, they said.

However, the benefits did not sufficiently outweigh the harms to justify recommending fluoroquinolone prophylaxis for all patients with solid tumors or lymphoma, according to the report from the expert panel.

Those harms could include antibiotic-associated adverse effects, emergence of resistance, and Clostridium difficile infections, they said.

Accordingly, they recommended fluoroquinolone prophylaxis for the high-risk patients, including most patients with acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) or those undergoing hematopoietic stem-cell transplantation (HSCT).

Similarly, the panel recommended that high-risk patients should receive antifungal prophylaxis with an oral triazole or parenteral echinocandin, while prophylaxis would not be routinely recommended for solid tumor patients.

By contrast, all patients undergoing chemotherapy for malignancy should receive yearly influenza vaccination with an inactivated quadrivalent vaccine, the panel said in its antiviral prophylaxis recommendations.

Family members, household contacts, and health care providers also should receive influenza vaccinations, said the panel, endorsing recommendations from the Centers for Disease Control and Prevention that were also cited in the 2013 ASCO guidelines.

Health care workers should follow hand hygiene and respiratory hygiene/cough etiquette to reduce risk of pathogen transmission, the panel said, endorsing CDC recommendations cited in the previous guideline.

However, the panel said they recommend against interventions such as neutropenic diet, footwear exchange, nutritional supplements, and surgical masks.

“Evidence of clinical benefit is lacking” for those interventions, they said.

Participants in the expert panel disclosed potential conflicts of interest related to Merck, Chimerix, GlyPharma Therapeutic, Pfizer, Cidara Therapeutics, Celgene, Astellas Pharma, Gilead Sciences, and Allergan, among other entities.
 

SOURCE: Taplitz RA et al. J Clin Oncol. 2018 Sept 4. doi: 10.1200/JCO.18.00374.

Health Canada has authorized use of tisagenlecleucel (Kymriah), the first chimeric antigen receptor (CAR) T-cell therapy to receive regulatory approval in Canada.

Tisagenlecleucel is approved to treat patients aged 3-25 years who have B-cell acute lymphoblastic leukemia (ALL) and relapsed after allogenic stem cell transplant (SCT) or are otherwise ineligible for SCT, have experienced second or later relapse, or have refractory disease.

Tisagenlecleucel is also approved in Canada to treat adults who have received two or more lines of systemic therapy and have relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high-grade B-cell lymphoma, or DLBCL arising from follicular lymphoma.

Novartis, the company marketing tisagenlecleucel, said it is working with qualified treatment centers in Canada to prepare for the delivery of tisagenlecleucel. Certification and training are underway at these centers and Novartis is enhancing manufacturing capacity to meet patient needs.

Tisagenlecleucel has been studied in a pair of phase 2 trials – JULIET and ELIANA.

JULIET enrolled 165 adults with relapsed/refractory DLBCL, 111 of whom received a single infusion of tisagenlecleucel.

The overall response rate was 52% and the complete response (CR) rate was 40%. The median duration of response was not reached with a median follow-up of 13.9 months. At last follow-up, none of the responders had gone on to SCT.

The 12-month overall survival (OS) rate was 49%; the median OS was 11.7 months. The median OS was not reached for patients in CR.

Within 8 weeks of tisagenlecleucel infusion, 22% of patients had developed grade 3/4 cytokine release syndrome.

These results were presented at the 2018 annual congress of the European Hematology Association in June.

The ELIANA trial included 75 children and young adults with relapsed/refractory ALL. All patients received a single infusion of tisagenlecleucel, and 72 received lymphodepleting chemotherapy.

The median duration of follow-up was 13.1 months. The overall remission rate was 81%, with 60% of patients achieving a CR and 21% achieving CR with incomplete hematologic recovery. All patients whose best response was CR with incomplete hematologic recovery were negative for minimal residual disease. The median duration of response was not met.

Eight patients proceeded to SCT while in remission. At last follow-up, four were still in remission, and four had unknown disease status.

At 6 months, the event-free survival rate was 73%, and the OS rate was 90%. At 12 months, the rates were 50% and 76%, respectively.

About 95% of patients had adverse events thought to be related to tisagenlecleucel. The incidence of treatment-related grade 3/4 adverse eventss was 73% (N Engl J Med 2018; 378:439-48).

[email protected]

Health Canada has authorized use of tisagenlecleucel (Kymriah), the first chimeric antigen receptor (CAR) T-cell therapy to receive regulatory approval in Canada.

Tisagenlecleucel is approved to treat patients aged 3-25 years who have B-cell acute lymphoblastic leukemia (ALL) and relapsed after allogenic stem cell transplant (SCT) or are otherwise ineligible for SCT, have experienced second or later relapse, or have refractory disease.

Tisagenlecleucel is also approved in Canada to treat adults who have received two or more lines of systemic therapy and have relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high-grade B-cell lymphoma, or DLBCL arising from follicular lymphoma.

Novartis, the company marketing tisagenlecleucel, said it is working with qualified treatment centers in Canada to prepare for the delivery of tisagenlecleucel. Certification and training are underway at these centers and Novartis is enhancing manufacturing capacity to meet patient needs.

Tisagenlecleucel has been studied in a pair of phase 2 trials – JULIET and ELIANA.

JULIET enrolled 165 adults with relapsed/refractory DLBCL, 111 of whom received a single infusion of tisagenlecleucel.

The overall response rate was 52% and the complete response (CR) rate was 40%. The median duration of response was not reached with a median follow-up of 13.9 months. At last follow-up, none of the responders had gone on to SCT.

The 12-month overall survival (OS) rate was 49%; the median OS was 11.7 months. The median OS was not reached for patients in CR.

Within 8 weeks of tisagenlecleucel infusion, 22% of patients had developed grade 3/4 cytokine release syndrome.

These results were presented at the 2018 annual congress of the European Hematology Association in June.

The ELIANA trial included 75 children and young adults with relapsed/refractory ALL. All patients received a single infusion of tisagenlecleucel, and 72 received lymphodepleting chemotherapy.

The median duration of follow-up was 13.1 months. The overall remission rate was 81%, with 60% of patients achieving a CR and 21% achieving CR with incomplete hematologic recovery. All patients whose best response was CR with incomplete hematologic recovery were negative for minimal residual disease. The median duration of response was not met.

Eight patients proceeded to SCT while in remission. At last follow-up, four were still in remission, and four had unknown disease status.

At 6 months, the event-free survival rate was 73%, and the OS rate was 90%. At 12 months, the rates were 50% and 76%, respectively.

About 95% of patients had adverse events thought to be related to tisagenlecleucel. The incidence of treatment-related grade 3/4 adverse eventss was 73% (N Engl J Med 2018; 378:439-48).

[email protected]

Health Canada has authorized use of tisagenlecleucel (Kymriah), the first chimeric antigen receptor (CAR) T-cell therapy to receive regulatory approval in Canada.

Tisagenlecleucel is approved to treat patients aged 3-25 years who have B-cell acute lymphoblastic leukemia (ALL) and relapsed after allogenic stem cell transplant (SCT) or are otherwise ineligible for SCT, have experienced second or later relapse, or have refractory disease.

Tisagenlecleucel is also approved in Canada to treat adults who have received two or more lines of systemic therapy and have relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high-grade B-cell lymphoma, or DLBCL arising from follicular lymphoma.

Novartis, the company marketing tisagenlecleucel, said it is working with qualified treatment centers in Canada to prepare for the delivery of tisagenlecleucel. Certification and training are underway at these centers and Novartis is enhancing manufacturing capacity to meet patient needs.

Tisagenlecleucel has been studied in a pair of phase 2 trials – JULIET and ELIANA.

JULIET enrolled 165 adults with relapsed/refractory DLBCL, 111 of whom received a single infusion of tisagenlecleucel.

The overall response rate was 52% and the complete response (CR) rate was 40%. The median duration of response was not reached with a median follow-up of 13.9 months. At last follow-up, none of the responders had gone on to SCT.

The 12-month overall survival (OS) rate was 49%; the median OS was 11.7 months. The median OS was not reached for patients in CR.

Within 8 weeks of tisagenlecleucel infusion, 22% of patients had developed grade 3/4 cytokine release syndrome.

These results were presented at the 2018 annual congress of the European Hematology Association in June.

The ELIANA trial included 75 children and young adults with relapsed/refractory ALL. All patients received a single infusion of tisagenlecleucel, and 72 received lymphodepleting chemotherapy.

The median duration of follow-up was 13.1 months. The overall remission rate was 81%, with 60% of patients achieving a CR and 21% achieving CR with incomplete hematologic recovery. All patients whose best response was CR with incomplete hematologic recovery were negative for minimal residual disease. The median duration of response was not met.

Eight patients proceeded to SCT while in remission. At last follow-up, four were still in remission, and four had unknown disease status.

At 6 months, the event-free survival rate was 73%, and the OS rate was 90%. At 12 months, the rates were 50% and 76%, respectively.

About 95% of patients had adverse events thought to be related to tisagenlecleucel. The incidence of treatment-related grade 3/4 adverse eventss was 73% (N Engl J Med 2018; 378:439-48).

[email protected]