ASH 2018

SAN DIEGO – A second-generation CD19-specific “armored” chimeric antigen receptor (CAR) T-cell construct was associated with high complete remission rates in diffuse large B-cell lymphoma (DLBCL) and indolent non-Hodgkin lymphoma (NHL) in a phase 1 trial.

Neil Osterweil/ MDedge News

The CAR T construct – labeled 1928z-41BBL – also induced “encouraging” complete remission rates in patients with chronic lymphocytic leukemia (CLL) with Richter’s transformation, reported Jae H. Park, MD, of Memorial Sloan Kettering Cancer Center (MSKCC), New York, and his colleagues.

“Interestingly and encouragingly, severe [cytokine release syndrome] was not seen and grade 3 neurotoxicity was observed in less than 10%, with no grade 4 neurotoxicity, so there appears to be a favorable side effect profile,” Dr. Park said at the annual meeting of the American Society of Hematology.

Just as armored cars are designed to protect their valuable contents from people with bad intent, armored CAR T cells are engineered to protect the modified T-cells from a hostile tumor microenvironment and simultaneously recruit non-modified T cells to the target to produce a more robust immune response against malignant cells.

MSKCC investigators had previously shown that in contrast to other CAR T-cell constructs, the 1928z-41BBL configuration, which consists of two signaling domains (CD28 and CD3zeta) and the 4-1BB ligand, hit the sweet spot between tumor-killing function and T-cell persistence (Cancer Cell. 2015 Oct 12;28[4]:415-28).

In the current study, they enrolled 35 adults with relapsed or refractory CD19-positive hematologic malignancies, 29 of whom eventually underwent CAR T-cell infusions. The treated population comprised 14 patients with CLL (4 of whom had Richter’s transformation), 9 with DLBCL, 5 with indolent NHL, and 1 with acute lymphoblastic leukemia.

The patients with CLL had received a median of 5.5 prior lines of therapy, including ibrutinib (Imbruvica) and venetoclax (Venclexta).

There were 15 complete remissions (CR), with CR rates of 78% in DLBCL, 20% in CLL, 67% in CLL with Richter’s transformation, 60% in patients with indolent NHL, as well as CR in the single patient with ALL.

There were eight partial remissions. One patient with CLL had stable disease, and four patients had disease progression (one patient each with DLBCL, CLL, CLL with Richter’s, and indolent NHL).

Dr. Park noted that T cells are being detected in peripheral blood more than 6 months after T-cell infusion.

There were no cases of severe cytokine release syndrome, defined as requiring vasopressors and/or mechanical ventilation for hypoxia, and just three cases of grade 3 neurotoxicity. There were no cases of grade 4 neurotoxicity, no deaths related to neurotoxicity, and no cases of cerebral edema – a serious complication that has been seen in earlier CAR T-cell studies.

Split or multiple infusions of CAR T cells or incorporation of the technique into earlier lines of therapy might generate higher response rates, Dr. Park said.

The study was supported by Juno Therapeutics. Dr. Park reported consulting for and research funding from Juno, and financial relationships with other companies.
 

SOURCE: Park JH et al. ASH 2018, Abstract 224.

SAN DIEGO – A second-generation CD19-specific “armored” chimeric antigen receptor (CAR) T-cell construct was associated with high complete remission rates in diffuse large B-cell lymphoma (DLBCL) and indolent non-Hodgkin lymphoma (NHL) in a phase 1 trial.

Neil Osterweil/ MDedge News

The CAR T construct – labeled 1928z-41BBL – also induced “encouraging” complete remission rates in patients with chronic lymphocytic leukemia (CLL) with Richter’s transformation, reported Jae H. Park, MD, of Memorial Sloan Kettering Cancer Center (MSKCC), New York, and his colleagues.

“Interestingly and encouragingly, severe [cytokine release syndrome] was not seen and grade 3 neurotoxicity was observed in less than 10%, with no grade 4 neurotoxicity, so there appears to be a favorable side effect profile,” Dr. Park said at the annual meeting of the American Society of Hematology.

Just as armored cars are designed to protect their valuable contents from people with bad intent, armored CAR T cells are engineered to protect the modified T-cells from a hostile tumor microenvironment and simultaneously recruit non-modified T cells to the target to produce a more robust immune response against malignant cells.

MSKCC investigators had previously shown that in contrast to other CAR T-cell constructs, the 1928z-41BBL configuration, which consists of two signaling domains (CD28 and CD3zeta) and the 4-1BB ligand, hit the sweet spot between tumor-killing function and T-cell persistence (Cancer Cell. 2015 Oct 12;28[4]:415-28).

In the current study, they enrolled 35 adults with relapsed or refractory CD19-positive hematologic malignancies, 29 of whom eventually underwent CAR T-cell infusions. The treated population comprised 14 patients with CLL (4 of whom had Richter’s transformation), 9 with DLBCL, 5 with indolent NHL, and 1 with acute lymphoblastic leukemia.

The patients with CLL had received a median of 5.5 prior lines of therapy, including ibrutinib (Imbruvica) and venetoclax (Venclexta).

There were 15 complete remissions (CR), with CR rates of 78% in DLBCL, 20% in CLL, 67% in CLL with Richter’s transformation, 60% in patients with indolent NHL, as well as CR in the single patient with ALL.

There were eight partial remissions. One patient with CLL had stable disease, and four patients had disease progression (one patient each with DLBCL, CLL, CLL with Richter’s, and indolent NHL).

Dr. Park noted that T cells are being detected in peripheral blood more than 6 months after T-cell infusion.

There were no cases of severe cytokine release syndrome, defined as requiring vasopressors and/or mechanical ventilation for hypoxia, and just three cases of grade 3 neurotoxicity. There were no cases of grade 4 neurotoxicity, no deaths related to neurotoxicity, and no cases of cerebral edema – a serious complication that has been seen in earlier CAR T-cell studies.

Split or multiple infusions of CAR T cells or incorporation of the technique into earlier lines of therapy might generate higher response rates, Dr. Park said.

The study was supported by Juno Therapeutics. Dr. Park reported consulting for and research funding from Juno, and financial relationships with other companies.
 

SOURCE: Park JH et al. ASH 2018, Abstract 224.

SAN DIEGO – A second-generation CD19-specific “armored” chimeric antigen receptor (CAR) T-cell construct was associated with high complete remission rates in diffuse large B-cell lymphoma (DLBCL) and indolent non-Hodgkin lymphoma (NHL) in a phase 1 trial.

Neil Osterweil/ MDedge News

The CAR T construct – labeled 1928z-41BBL – also induced “encouraging” complete remission rates in patients with chronic lymphocytic leukemia (CLL) with Richter’s transformation, reported Jae H. Park, MD, of Memorial Sloan Kettering Cancer Center (MSKCC), New York, and his colleagues.

“Interestingly and encouragingly, severe [cytokine release syndrome] was not seen and grade 3 neurotoxicity was observed in less than 10%, with no grade 4 neurotoxicity, so there appears to be a favorable side effect profile,” Dr. Park said at the annual meeting of the American Society of Hematology.

Just as armored cars are designed to protect their valuable contents from people with bad intent, armored CAR T cells are engineered to protect the modified T-cells from a hostile tumor microenvironment and simultaneously recruit non-modified T cells to the target to produce a more robust immune response against malignant cells.

MSKCC investigators had previously shown that in contrast to other CAR T-cell constructs, the 1928z-41BBL configuration, which consists of two signaling domains (CD28 and CD3zeta) and the 4-1BB ligand, hit the sweet spot between tumor-killing function and T-cell persistence (Cancer Cell. 2015 Oct 12;28[4]:415-28).

In the current study, they enrolled 35 adults with relapsed or refractory CD19-positive hematologic malignancies, 29 of whom eventually underwent CAR T-cell infusions. The treated population comprised 14 patients with CLL (4 of whom had Richter’s transformation), 9 with DLBCL, 5 with indolent NHL, and 1 with acute lymphoblastic leukemia.

The patients with CLL had received a median of 5.5 prior lines of therapy, including ibrutinib (Imbruvica) and venetoclax (Venclexta).

There were 15 complete remissions (CR), with CR rates of 78% in DLBCL, 20% in CLL, 67% in CLL with Richter’s transformation, 60% in patients with indolent NHL, as well as CR in the single patient with ALL.

There were eight partial remissions. One patient with CLL had stable disease, and four patients had disease progression (one patient each with DLBCL, CLL, CLL with Richter’s, and indolent NHL).

Dr. Park noted that T cells are being detected in peripheral blood more than 6 months after T-cell infusion.

There were no cases of severe cytokine release syndrome, defined as requiring vasopressors and/or mechanical ventilation for hypoxia, and just three cases of grade 3 neurotoxicity. There were no cases of grade 4 neurotoxicity, no deaths related to neurotoxicity, and no cases of cerebral edema – a serious complication that has been seen in earlier CAR T-cell studies.

Split or multiple infusions of CAR T cells or incorporation of the technique into earlier lines of therapy might generate higher response rates, Dr. Park said.

The study was supported by Juno Therapeutics. Dr. Park reported consulting for and research funding from Juno, and financial relationships with other companies.
 

SOURCE: Park JH et al. ASH 2018, Abstract 224.

SAN DIEGO – The majority of pediatric patients with mixed phenotype acute leukemia (MPAL) who were treated with acute lymphoblastic leukemia (ALL)–directed chemotherapy achieved a minimum residual disease (MRD)–negative complete response by the end of consolidation, according to findings from a multicenter retrospective cohort study.

Sharon Worcester/MDedge News

The cohort included 94 patients aged 1-21 years who met strict World Health Organization MPAL criteria and were treated between 2008 and 2016 at one of six U.S. institutions. Most had B/myeloid phenotype (89%), and 87 patients were treated with an ALL regimen, Etan Orgel, MD, reported at the annual meeting of the American Society of Hematology.

Of those 87 patients, 81 (93%) experienced an end-of-induction (EOI) complete response. One patient died during induction and six had induction failures, defined as either disease progression before EOI (two patients) or EOI MRD of 5% or greater (three patients), said Dr. Orgel of the University of Southern California, Los Angeles, and Children’s Hospital Los Angeles.

The MRD-negative rates, defined as MRD less than 0.01%, were 70% at EOI and 86% at EOI or end of consolidation (EOC); 12 of 14 patients who were MRD positive at EOI and continued on ALL therapy achieved an EOC MRD-negative complete response, including 8 of 8 with EOI MRD of 0.01%-0.09% and 4 of 6 with EOI MRD of 1% or greater.

Event-free survival at 5 years in the 78 patients without hematopoietic stem cell transplant at first remission was 75%, and 5-year overall survival was 89%, “thus demonstrating that, for a majority of patients, transplant in first remission may not be necessary,” Dr. Orgel said. “This is very different from the approach used at many adult centers and many of the adult recommendations.”

Overall 5-year EOI event-free survival was 80% in the 59 patients who were MRD negative at EOI, and 13% in 25 patients who were MRD-positive at EOI. The corresponding overall survival rates were 91% and 84%.

Overall 5-year EOC event-free survival was 77% in 74 patients who were MRD negative at EOC and was unavailable in 3 patients who were MRD positive at EOC, although all three were salvaged. The corresponding EOC overall survival rates were 89% and “not available,” Dr. Orgel reported.

Multivariable analysis confirmed the predictive value of MRD at EOI (hazard ratio for event-free survival and overall survival, 3.77 and 3.54, respectively).

Of note, there was a possible trend toward earlier failure and a trend toward worse overall survival (HR, 4.49, P = .074) for T-lineage–containing MPAL.

“That indicates that this might be a group that needs careful scrutiny of which form of ALL therapy they receive,” he said.

MRD in pediatric MPAL is rare. Recent studies of MPAL biology show areas of similarity with ALL and AML, and while this could eventually help further subcategorize or classify the disease and lead to biology-driven therapies, it is important to know how to treat the disease today, Dr. Orgel said.

The evolving consensus is that ALL therapy is adequate for most MPAL, but there is no established threshold for MRD to enable a risk-stratified MPAL approach, he added.

The current findings suggest that ALL therapy – without hematopoietic stem cell transplant – may be sufficient to treat most patients with pediatric MPAL, Dr. Orgen reported, noting that clinical trials are necessary to prospectively validate MRD thresholds at EOI and EOC and to establish the threshold for favorable survival.

“Future research should explore either intensification of therapy or different therapies for patients with persistent MRD,” he said.

Dr. Orgel reported having no financial disclosures.

[email protected]

SOURCE: Oberley M et al. ASH 2018, Abstract 558.

SAN DIEGO – The majority of pediatric patients with mixed phenotype acute leukemia (MPAL) who were treated with acute lymphoblastic leukemia (ALL)–directed chemotherapy achieved a minimum residual disease (MRD)–negative complete response by the end of consolidation, according to findings from a multicenter retrospective cohort study.

Sharon Worcester/MDedge News

The cohort included 94 patients aged 1-21 years who met strict World Health Organization MPAL criteria and were treated between 2008 and 2016 at one of six U.S. institutions. Most had B/myeloid phenotype (89%), and 87 patients were treated with an ALL regimen, Etan Orgel, MD, reported at the annual meeting of the American Society of Hematology.

Of those 87 patients, 81 (93%) experienced an end-of-induction (EOI) complete response. One patient died during induction and six had induction failures, defined as either disease progression before EOI (two patients) or EOI MRD of 5% or greater (three patients), said Dr. Orgel of the University of Southern California, Los Angeles, and Children’s Hospital Los Angeles.

The MRD-negative rates, defined as MRD less than 0.01%, were 70% at EOI and 86% at EOI or end of consolidation (EOC); 12 of 14 patients who were MRD positive at EOI and continued on ALL therapy achieved an EOC MRD-negative complete response, including 8 of 8 with EOI MRD of 0.01%-0.09% and 4 of 6 with EOI MRD of 1% or greater.

Event-free survival at 5 years in the 78 patients without hematopoietic stem cell transplant at first remission was 75%, and 5-year overall survival was 89%, “thus demonstrating that, for a majority of patients, transplant in first remission may not be necessary,” Dr. Orgel said. “This is very different from the approach used at many adult centers and many of the adult recommendations.”

Overall 5-year EOI event-free survival was 80% in the 59 patients who were MRD negative at EOI, and 13% in 25 patients who were MRD-positive at EOI. The corresponding overall survival rates were 91% and 84%.

Overall 5-year EOC event-free survival was 77% in 74 patients who were MRD negative at EOC and was unavailable in 3 patients who were MRD positive at EOC, although all three were salvaged. The corresponding EOC overall survival rates were 89% and “not available,” Dr. Orgel reported.

Multivariable analysis confirmed the predictive value of MRD at EOI (hazard ratio for event-free survival and overall survival, 3.77 and 3.54, respectively).

Of note, there was a possible trend toward earlier failure and a trend toward worse overall survival (HR, 4.49, P = .074) for T-lineage–containing MPAL.

“That indicates that this might be a group that needs careful scrutiny of which form of ALL therapy they receive,” he said.

MRD in pediatric MPAL is rare. Recent studies of MPAL biology show areas of similarity with ALL and AML, and while this could eventually help further subcategorize or classify the disease and lead to biology-driven therapies, it is important to know how to treat the disease today, Dr. Orgel said.

The evolving consensus is that ALL therapy is adequate for most MPAL, but there is no established threshold for MRD to enable a risk-stratified MPAL approach, he added.

The current findings suggest that ALL therapy – without hematopoietic stem cell transplant – may be sufficient to treat most patients with pediatric MPAL, Dr. Orgen reported, noting that clinical trials are necessary to prospectively validate MRD thresholds at EOI and EOC and to establish the threshold for favorable survival.

“Future research should explore either intensification of therapy or different therapies for patients with persistent MRD,” he said.

Dr. Orgel reported having no financial disclosures.

[email protected]

SOURCE: Oberley M et al. ASH 2018, Abstract 558.

SAN DIEGO – The majority of pediatric patients with mixed phenotype acute leukemia (MPAL) who were treated with acute lymphoblastic leukemia (ALL)–directed chemotherapy achieved a minimum residual disease (MRD)–negative complete response by the end of consolidation, according to findings from a multicenter retrospective cohort study.

Sharon Worcester/MDedge News

The cohort included 94 patients aged 1-21 years who met strict World Health Organization MPAL criteria and were treated between 2008 and 2016 at one of six U.S. institutions. Most had B/myeloid phenotype (89%), and 87 patients were treated with an ALL regimen, Etan Orgel, MD, reported at the annual meeting of the American Society of Hematology.

Of those 87 patients, 81 (93%) experienced an end-of-induction (EOI) complete response. One patient died during induction and six had induction failures, defined as either disease progression before EOI (two patients) or EOI MRD of 5% or greater (three patients), said Dr. Orgel of the University of Southern California, Los Angeles, and Children’s Hospital Los Angeles.

The MRD-negative rates, defined as MRD less than 0.01%, were 70% at EOI and 86% at EOI or end of consolidation (EOC); 12 of 14 patients who were MRD positive at EOI and continued on ALL therapy achieved an EOC MRD-negative complete response, including 8 of 8 with EOI MRD of 0.01%-0.09% and 4 of 6 with EOI MRD of 1% or greater.

Event-free survival at 5 years in the 78 patients without hematopoietic stem cell transplant at first remission was 75%, and 5-year overall survival was 89%, “thus demonstrating that, for a majority of patients, transplant in first remission may not be necessary,” Dr. Orgel said. “This is very different from the approach used at many adult centers and many of the adult recommendations.”

Overall 5-year EOI event-free survival was 80% in the 59 patients who were MRD negative at EOI, and 13% in 25 patients who were MRD-positive at EOI. The corresponding overall survival rates were 91% and 84%.

Overall 5-year EOC event-free survival was 77% in 74 patients who were MRD negative at EOC and was unavailable in 3 patients who were MRD positive at EOC, although all three were salvaged. The corresponding EOC overall survival rates were 89% and “not available,” Dr. Orgel reported.

Multivariable analysis confirmed the predictive value of MRD at EOI (hazard ratio for event-free survival and overall survival, 3.77 and 3.54, respectively).

Of note, there was a possible trend toward earlier failure and a trend toward worse overall survival (HR, 4.49, P = .074) for T-lineage–containing MPAL.

“That indicates that this might be a group that needs careful scrutiny of which form of ALL therapy they receive,” he said.

MRD in pediatric MPAL is rare. Recent studies of MPAL biology show areas of similarity with ALL and AML, and while this could eventually help further subcategorize or classify the disease and lead to biology-driven therapies, it is important to know how to treat the disease today, Dr. Orgel said.

The evolving consensus is that ALL therapy is adequate for most MPAL, but there is no established threshold for MRD to enable a risk-stratified MPAL approach, he added.

The current findings suggest that ALL therapy – without hematopoietic stem cell transplant – may be sufficient to treat most patients with pediatric MPAL, Dr. Orgen reported, noting that clinical trials are necessary to prospectively validate MRD thresholds at EOI and EOC and to establish the threshold for favorable survival.

“Future research should explore either intensification of therapy or different therapies for patients with persistent MRD,” he said.

Dr. Orgel reported having no financial disclosures.

[email protected]

SOURCE: Oberley M et al. ASH 2018, Abstract 558.

SAN DIEGO – For patients 65 years or younger with mantle cell lymphoma (MCL) who have undergone autologous stem cell transplantation (ASCT), maintenance therapy with lenalidomide (Revlimid) can significantly improve progression-free survival (PFS), suggest results of the phase, 3 randomized MCL0208 trial.

Neil Osterweil/MDedge News

After a median follow-up of 39 months, the 3-year PFS in an intention-to-treat analysis was 80% for patients treated with ASCT and lenalidomide maintenance, compared with 64% for patients treated with ASCT alone, reported Marco Ladetto, MD, of Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo in Alessandria, Italy.

“Lenalidomide maintenance after autologous stem cell transplant has substantial clinical activity in mantle cell lymphoma in terms of progression-free survival,” he said at the annual meeting of the American Society of Hematology. “Follow-up is still too short for meaningful overall survival considerations.”

Dr. Ladetto and his colleagues at centers in Italy and Portugal enrolled patients aged 18-65 years with previously untreated MCL stage III or IV, or stage II with bulky disease (5 cm or greater), and good performance status.

The patients first underwent induction with three cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, and prednisone), which was followed by treatment with rituximab plus high-dose cyclophosphamide and two cycles of rituximab with high-dose cytarabine. Stem cells were collected after the first course of the latter regimen.

The patients then underwent conditioning with BEAM (carmustine, etoposide, cytarabine, melphalan) and ASCT.

Following ASCT, patients with complete or partial remissions were randomized either to maintenance therapy with lenalidomide 15 mg for 21 of 28 days for each cycle or to observation.

Of the 303 patients initially enrolled, 248 went on to ASCT, and 205 went on to randomization – 104 assigned to maintenance and 101 assigned to observation.

A total of 52 patients completed 2 years of maintenance: Of the rest, 2 patients died from toxicities (thrombotic thrombocytopenic purpura and pneumonia), 7 had disease progression, 41 dropped out for nonprogression reasons, and 2 patients were still in maintenance at the time of the data cutoff. In this arm, 6 of 8 patients with partial responses converted to complete responses by the end of maintenance. More than a quarter of patients (28%) received less than 25% of the planned lenalidomide dose.

In the observation arm, 1 patient died from pneumonia, 20 had disease progression, 3 were lost to follow-up, 6 were still under observation, and 71 completed observation. In this arm, 1 of 4 patients with a partial response converted to a complete response at the end of the observation period.

Despite suboptimal dosing in a large proportion of patients, the PFS primary endpoint showed significant benefit for lenalidomide, with an unstratified hazard ratio of 0.52 (P = .015) and a stratified HR of 0.51 (P = .013).

At a median follow-up of 39 months from randomization, 3-year overall survival (OS) rates were 93% with lenalidomide and 86% with observation, a difference that was not statistically significant.

Grade 3 or 4 hematologic toxicities occurred in 63% of patients in the lenalidomide arm, compared with 11% in the observation arm. The respective rates of granulocytopenia were 59% vs. 10%. Nonhematological grade 3 toxicity was comparable in the two arms except for grade 3 or 4 infections, which were more common with lenalidomide. Seven patients in the lenalidomide arm and three patients in the observation arm developed second cancers.

Dr. Ladetto noted that difficulties in delivering the planned dose of lenalidomide may have been caused by an already-stressed hematopoietic compartment; he commented that the question of the relative benefit of a fixed lenalidomide schedule or an until-progression approach still needs to be answered.

Additionally, the induction schedule used in the trial, while feasible, is not superior to “less cumbersome and possibly less toxic regimens,” he said.

The study was supported by the Italian Lymphoma Foundation (Fondazione Italiana Linfomi) with the European Mantle Cell Lymphoma Network. Dr. Ladetto reported honoraria from Roche, Celgene, Acerta, Janssen, AbbVie, and Sandoz, as well as off-label use of lenalidomide.

SOURCE: Ladetto M et al. ASH 2018, Abstract 401.

SAN DIEGO – For patients 65 years or younger with mantle cell lymphoma (MCL) who have undergone autologous stem cell transplantation (ASCT), maintenance therapy with lenalidomide (Revlimid) can significantly improve progression-free survival (PFS), suggest results of the phase, 3 randomized MCL0208 trial.

Neil Osterweil/MDedge News

After a median follow-up of 39 months, the 3-year PFS in an intention-to-treat analysis was 80% for patients treated with ASCT and lenalidomide maintenance, compared with 64% for patients treated with ASCT alone, reported Marco Ladetto, MD, of Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo in Alessandria, Italy.

“Lenalidomide maintenance after autologous stem cell transplant has substantial clinical activity in mantle cell lymphoma in terms of progression-free survival,” he said at the annual meeting of the American Society of Hematology. “Follow-up is still too short for meaningful overall survival considerations.”

Dr. Ladetto and his colleagues at centers in Italy and Portugal enrolled patients aged 18-65 years with previously untreated MCL stage III or IV, or stage II with bulky disease (5 cm or greater), and good performance status.

The patients first underwent induction with three cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, and prednisone), which was followed by treatment with rituximab plus high-dose cyclophosphamide and two cycles of rituximab with high-dose cytarabine. Stem cells were collected after the first course of the latter regimen.

The patients then underwent conditioning with BEAM (carmustine, etoposide, cytarabine, melphalan) and ASCT.

Following ASCT, patients with complete or partial remissions were randomized either to maintenance therapy with lenalidomide 15 mg for 21 of 28 days for each cycle or to observation.

Of the 303 patients initially enrolled, 248 went on to ASCT, and 205 went on to randomization – 104 assigned to maintenance and 101 assigned to observation.

A total of 52 patients completed 2 years of maintenance: Of the rest, 2 patients died from toxicities (thrombotic thrombocytopenic purpura and pneumonia), 7 had disease progression, 41 dropped out for nonprogression reasons, and 2 patients were still in maintenance at the time of the data cutoff. In this arm, 6 of 8 patients with partial responses converted to complete responses by the end of maintenance. More than a quarter of patients (28%) received less than 25% of the planned lenalidomide dose.

In the observation arm, 1 patient died from pneumonia, 20 had disease progression, 3 were lost to follow-up, 6 were still under observation, and 71 completed observation. In this arm, 1 of 4 patients with a partial response converted to a complete response at the end of the observation period.

Despite suboptimal dosing in a large proportion of patients, the PFS primary endpoint showed significant benefit for lenalidomide, with an unstratified hazard ratio of 0.52 (P = .015) and a stratified HR of 0.51 (P = .013).

At a median follow-up of 39 months from randomization, 3-year overall survival (OS) rates were 93% with lenalidomide and 86% with observation, a difference that was not statistically significant.

Grade 3 or 4 hematologic toxicities occurred in 63% of patients in the lenalidomide arm, compared with 11% in the observation arm. The respective rates of granulocytopenia were 59% vs. 10%. Nonhematological grade 3 toxicity was comparable in the two arms except for grade 3 or 4 infections, which were more common with lenalidomide. Seven patients in the lenalidomide arm and three patients in the observation arm developed second cancers.

Dr. Ladetto noted that difficulties in delivering the planned dose of lenalidomide may have been caused by an already-stressed hematopoietic compartment; he commented that the question of the relative benefit of a fixed lenalidomide schedule or an until-progression approach still needs to be answered.

Additionally, the induction schedule used in the trial, while feasible, is not superior to “less cumbersome and possibly less toxic regimens,” he said.

The study was supported by the Italian Lymphoma Foundation (Fondazione Italiana Linfomi) with the European Mantle Cell Lymphoma Network. Dr. Ladetto reported honoraria from Roche, Celgene, Acerta, Janssen, AbbVie, and Sandoz, as well as off-label use of lenalidomide.

SOURCE: Ladetto M et al. ASH 2018, Abstract 401.

SAN DIEGO – For patients 65 years or younger with mantle cell lymphoma (MCL) who have undergone autologous stem cell transplantation (ASCT), maintenance therapy with lenalidomide (Revlimid) can significantly improve progression-free survival (PFS), suggest results of the phase, 3 randomized MCL0208 trial.

Neil Osterweil/MDedge News

After a median follow-up of 39 months, the 3-year PFS in an intention-to-treat analysis was 80% for patients treated with ASCT and lenalidomide maintenance, compared with 64% for patients treated with ASCT alone, reported Marco Ladetto, MD, of Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo in Alessandria, Italy.

“Lenalidomide maintenance after autologous stem cell transplant has substantial clinical activity in mantle cell lymphoma in terms of progression-free survival,” he said at the annual meeting of the American Society of Hematology. “Follow-up is still too short for meaningful overall survival considerations.”

Dr. Ladetto and his colleagues at centers in Italy and Portugal enrolled patients aged 18-65 years with previously untreated MCL stage III or IV, or stage II with bulky disease (5 cm or greater), and good performance status.

The patients first underwent induction with three cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, and prednisone), which was followed by treatment with rituximab plus high-dose cyclophosphamide and two cycles of rituximab with high-dose cytarabine. Stem cells were collected after the first course of the latter regimen.

The patients then underwent conditioning with BEAM (carmustine, etoposide, cytarabine, melphalan) and ASCT.

Following ASCT, patients with complete or partial remissions were randomized either to maintenance therapy with lenalidomide 15 mg for 21 of 28 days for each cycle or to observation.

Of the 303 patients initially enrolled, 248 went on to ASCT, and 205 went on to randomization – 104 assigned to maintenance and 101 assigned to observation.

A total of 52 patients completed 2 years of maintenance: Of the rest, 2 patients died from toxicities (thrombotic thrombocytopenic purpura and pneumonia), 7 had disease progression, 41 dropped out for nonprogression reasons, and 2 patients were still in maintenance at the time of the data cutoff. In this arm, 6 of 8 patients with partial responses converted to complete responses by the end of maintenance. More than a quarter of patients (28%) received less than 25% of the planned lenalidomide dose.

In the observation arm, 1 patient died from pneumonia, 20 had disease progression, 3 were lost to follow-up, 6 were still under observation, and 71 completed observation. In this arm, 1 of 4 patients with a partial response converted to a complete response at the end of the observation period.

Despite suboptimal dosing in a large proportion of patients, the PFS primary endpoint showed significant benefit for lenalidomide, with an unstratified hazard ratio of 0.52 (P = .015) and a stratified HR of 0.51 (P = .013).

At a median follow-up of 39 months from randomization, 3-year overall survival (OS) rates were 93% with lenalidomide and 86% with observation, a difference that was not statistically significant.

Grade 3 or 4 hematologic toxicities occurred in 63% of patients in the lenalidomide arm, compared with 11% in the observation arm. The respective rates of granulocytopenia were 59% vs. 10%. Nonhematological grade 3 toxicity was comparable in the two arms except for grade 3 or 4 infections, which were more common with lenalidomide. Seven patients in the lenalidomide arm and three patients in the observation arm developed second cancers.

Dr. Ladetto noted that difficulties in delivering the planned dose of lenalidomide may have been caused by an already-stressed hematopoietic compartment; he commented that the question of the relative benefit of a fixed lenalidomide schedule or an until-progression approach still needs to be answered.

Additionally, the induction schedule used in the trial, while feasible, is not superior to “less cumbersome and possibly less toxic regimens,” he said.

The study was supported by the Italian Lymphoma Foundation (Fondazione Italiana Linfomi) with the European Mantle Cell Lymphoma Network. Dr. Ladetto reported honoraria from Roche, Celgene, Acerta, Janssen, AbbVie, and Sandoz, as well as off-label use of lenalidomide.

SOURCE: Ladetto M et al. ASH 2018, Abstract 401.

Single-agent therapy with quizartinib slightly but significantly prolonged survival – compared with salvage chemotherapy – for patients with relapsed/refractory acute myeloid leukemia (AML) bearing the FLT3-ITD mutation, results of the phase 3 randomized QuANTUM-R trial showed.

Neil Osterweil/MDedge News

Median overall survival (OS), the trial’s primary endpoint, was 6.2 months for 245 patients randomized to quizartinib, compared with 4.7 months for 122 patients assigned to salvage chemotherapy, a difference that translated into a hazard ratio (HR) for death of 0.76 (P = .0177), reported Jorge E. Cortes, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“This study is the first study that demonstrates in a randomized fashion an overall survival benefit in the salvage setting for patients with FLT-3 mutated refractory or relapsed AML,” he said at the annual meeting of the American Society of Hematology. “I will also add that these results you saw here are very consistent with all the trials previously with quizartinib with more than 1,000 patients treated.”

Quizartinib, a tyrosine kinase inhibitor (TKI), has previously been shown to be associated with higher response rates among patients with AML bearing the FLT3-ITD mutation than in patients with AML without the deleterious mutation.

Investigators in the QuANTUM-R trial enrolled 367 adults with FTL3-ITD mutated AML that was refractory to the most recent line of therapy or had relapsed within 6 months of first remission, with or without hematopoietic stem cell transplant (HSCT).

The patients had all received at least one cycle of standard-dose induction therapy containing an anthracycline or mitoxantrone, and had a 3% or greater FLT3-ITD allelic ratio in their AML cells.

The patients were randomly assigned on a 2:1 basis to receive either quizartinib or salvage chemotherapy. Quizartinib was dosed 30 mg per day for 15 days, which could be titrated upward to 60 mg daily if the corrected QT interval by Fredericia (QTcF) was 450 ms or less on day 16.

Chemotherapy was the investigator’s choice of one of three specified regimens: either low-dose cytarabine (LoDAC); mitoxantrone, etoposide, and intermediate-dose cytarabine (MEC); or fludarabine, cytarabine, and granulocyte-colony stimulating factor (G-CSF) with idarubicin (FLAG-IDA). Up to two cycles of MEC or FLAG-IDA were permitted; quizartinib and LoDAC were given until lack of benefit, unacceptable toxicity, or until the patient went on to HSCT.

The analysis was by intention-to-treat. In the quizartinib arm, 241 of the 245 randomized patients (98.4%) received treatment. In the chemotherapy arm, 94 of 122 randomized patients (77%) received chemotherapy. Of this group, 22 received LoDAC, 25 received MEC, and 47 received FLAG-IDA.

The median treatment duration was 97 days in the quizartinib arm versus 28 days (one cycle) in the chemotherapy arm.

The 1-year overall survival rate was 27% for patients assigned to quizartinib, compared with 20% for patients assigned to chemotherapy.

An analysis of OS by subgroup indicated a trend or significant benefit for quizartinib in all categories, including age over or under 65 years, sex, low or high-intensity chemotherapy, response to prior therapy, FLT3 variant allele frequency, prior allogenic HSCT, and AML risk score.

For the secondary endpoint of event-free survival in the ITT population, there was no significant difference between the study arms. In a per-protocol analysis, however, median event-free survival was better with quizartinib, at 1.4 months versus 0.0 months (P = .006).

In all, 32% of patients assigned to quizartinib went on to HSCT, compared with 12% of patients randomized to chemotherapy.

Rates of treatment-emergent adverse events (TEAEs) were similar between the study arms, despite higher total drug exposure in patients randomized to quizartinib. The most frequent grade 3 or greater TEAEs in each arm were infections and cytopenia-related events.

Two patients discontinued quizartinib due to QTcF prolongation. Grade 3 QTcF (greater than 500 ms) occurred in 3% of patients treated with quizartinib, but no grade 4 cases were seen.

The adverse event profile for patients who resumed quizartinib following HSCT was similar to that of patients who received the drug pretransplant.

The combination of standard chemotherapy, with or without quizartinib, is currently being explored in the phase 3 QuANTUM-First trial, Dr. Cortes said.

Daiichi Sankyo sponsored the trial. Dr. Cortes reported financial relationships with Daiichi Sankyo, Pfizer, Arog, Astellas Pharma, and Novartis.

SOURCE: Cortes JE et al. ASH 2018, Abstract 563.

Single-agent therapy with quizartinib slightly but significantly prolonged survival – compared with salvage chemotherapy – for patients with relapsed/refractory acute myeloid leukemia (AML) bearing the FLT3-ITD mutation, results of the phase 3 randomized QuANTUM-R trial showed.

Neil Osterweil/MDedge News

Median overall survival (OS), the trial’s primary endpoint, was 6.2 months for 245 patients randomized to quizartinib, compared with 4.7 months for 122 patients assigned to salvage chemotherapy, a difference that translated into a hazard ratio (HR) for death of 0.76 (P = .0177), reported Jorge E. Cortes, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“This study is the first study that demonstrates in a randomized fashion an overall survival benefit in the salvage setting for patients with FLT-3 mutated refractory or relapsed AML,” he said at the annual meeting of the American Society of Hematology. “I will also add that these results you saw here are very consistent with all the trials previously with quizartinib with more than 1,000 patients treated.”

Quizartinib, a tyrosine kinase inhibitor (TKI), has previously been shown to be associated with higher response rates among patients with AML bearing the FLT3-ITD mutation than in patients with AML without the deleterious mutation.

Investigators in the QuANTUM-R trial enrolled 367 adults with FTL3-ITD mutated AML that was refractory to the most recent line of therapy or had relapsed within 6 months of first remission, with or without hematopoietic stem cell transplant (HSCT).

The patients had all received at least one cycle of standard-dose induction therapy containing an anthracycline or mitoxantrone, and had a 3% or greater FLT3-ITD allelic ratio in their AML cells.

The patients were randomly assigned on a 2:1 basis to receive either quizartinib or salvage chemotherapy. Quizartinib was dosed 30 mg per day for 15 days, which could be titrated upward to 60 mg daily if the corrected QT interval by Fredericia (QTcF) was 450 ms or less on day 16.

Chemotherapy was the investigator’s choice of one of three specified regimens: either low-dose cytarabine (LoDAC); mitoxantrone, etoposide, and intermediate-dose cytarabine (MEC); or fludarabine, cytarabine, and granulocyte-colony stimulating factor (G-CSF) with idarubicin (FLAG-IDA). Up to two cycles of MEC or FLAG-IDA were permitted; quizartinib and LoDAC were given until lack of benefit, unacceptable toxicity, or until the patient went on to HSCT.

The analysis was by intention-to-treat. In the quizartinib arm, 241 of the 245 randomized patients (98.4%) received treatment. In the chemotherapy arm, 94 of 122 randomized patients (77%) received chemotherapy. Of this group, 22 received LoDAC, 25 received MEC, and 47 received FLAG-IDA.

The median treatment duration was 97 days in the quizartinib arm versus 28 days (one cycle) in the chemotherapy arm.

The 1-year overall survival rate was 27% for patients assigned to quizartinib, compared with 20% for patients assigned to chemotherapy.

An analysis of OS by subgroup indicated a trend or significant benefit for quizartinib in all categories, including age over or under 65 years, sex, low or high-intensity chemotherapy, response to prior therapy, FLT3 variant allele frequency, prior allogenic HSCT, and AML risk score.

For the secondary endpoint of event-free survival in the ITT population, there was no significant difference between the study arms. In a per-protocol analysis, however, median event-free survival was better with quizartinib, at 1.4 months versus 0.0 months (P = .006).

In all, 32% of patients assigned to quizartinib went on to HSCT, compared with 12% of patients randomized to chemotherapy.

Rates of treatment-emergent adverse events (TEAEs) were similar between the study arms, despite higher total drug exposure in patients randomized to quizartinib. The most frequent grade 3 or greater TEAEs in each arm were infections and cytopenia-related events.

Two patients discontinued quizartinib due to QTcF prolongation. Grade 3 QTcF (greater than 500 ms) occurred in 3% of patients treated with quizartinib, but no grade 4 cases were seen.

The adverse event profile for patients who resumed quizartinib following HSCT was similar to that of patients who received the drug pretransplant.

The combination of standard chemotherapy, with or without quizartinib, is currently being explored in the phase 3 QuANTUM-First trial, Dr. Cortes said.

Daiichi Sankyo sponsored the trial. Dr. Cortes reported financial relationships with Daiichi Sankyo, Pfizer, Arog, Astellas Pharma, and Novartis.

SOURCE: Cortes JE et al. ASH 2018, Abstract 563.

Single-agent therapy with quizartinib slightly but significantly prolonged survival – compared with salvage chemotherapy – for patients with relapsed/refractory acute myeloid leukemia (AML) bearing the FLT3-ITD mutation, results of the phase 3 randomized QuANTUM-R trial showed.

Neil Osterweil/MDedge News

Median overall survival (OS), the trial’s primary endpoint, was 6.2 months for 245 patients randomized to quizartinib, compared with 4.7 months for 122 patients assigned to salvage chemotherapy, a difference that translated into a hazard ratio (HR) for death of 0.76 (P = .0177), reported Jorge E. Cortes, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“This study is the first study that demonstrates in a randomized fashion an overall survival benefit in the salvage setting for patients with FLT-3 mutated refractory or relapsed AML,” he said at the annual meeting of the American Society of Hematology. “I will also add that these results you saw here are very consistent with all the trials previously with quizartinib with more than 1,000 patients treated.”

Quizartinib, a tyrosine kinase inhibitor (TKI), has previously been shown to be associated with higher response rates among patients with AML bearing the FLT3-ITD mutation than in patients with AML without the deleterious mutation.

Investigators in the QuANTUM-R trial enrolled 367 adults with FTL3-ITD mutated AML that was refractory to the most recent line of therapy or had relapsed within 6 months of first remission, with or without hematopoietic stem cell transplant (HSCT).

The patients had all received at least one cycle of standard-dose induction therapy containing an anthracycline or mitoxantrone, and had a 3% or greater FLT3-ITD allelic ratio in their AML cells.

The patients were randomly assigned on a 2:1 basis to receive either quizartinib or salvage chemotherapy. Quizartinib was dosed 30 mg per day for 15 days, which could be titrated upward to 60 mg daily if the corrected QT interval by Fredericia (QTcF) was 450 ms or less on day 16.

Chemotherapy was the investigator’s choice of one of three specified regimens: either low-dose cytarabine (LoDAC); mitoxantrone, etoposide, and intermediate-dose cytarabine (MEC); or fludarabine, cytarabine, and granulocyte-colony stimulating factor (G-CSF) with idarubicin (FLAG-IDA). Up to two cycles of MEC or FLAG-IDA were permitted; quizartinib and LoDAC were given until lack of benefit, unacceptable toxicity, or until the patient went on to HSCT.

The analysis was by intention-to-treat. In the quizartinib arm, 241 of the 245 randomized patients (98.4%) received treatment. In the chemotherapy arm, 94 of 122 randomized patients (77%) received chemotherapy. Of this group, 22 received LoDAC, 25 received MEC, and 47 received FLAG-IDA.

The median treatment duration was 97 days in the quizartinib arm versus 28 days (one cycle) in the chemotherapy arm.

The 1-year overall survival rate was 27% for patients assigned to quizartinib, compared with 20% for patients assigned to chemotherapy.

An analysis of OS by subgroup indicated a trend or significant benefit for quizartinib in all categories, including age over or under 65 years, sex, low or high-intensity chemotherapy, response to prior therapy, FLT3 variant allele frequency, prior allogenic HSCT, and AML risk score.

For the secondary endpoint of event-free survival in the ITT population, there was no significant difference between the study arms. In a per-protocol analysis, however, median event-free survival was better with quizartinib, at 1.4 months versus 0.0 months (P = .006).

In all, 32% of patients assigned to quizartinib went on to HSCT, compared with 12% of patients randomized to chemotherapy.

Rates of treatment-emergent adverse events (TEAEs) were similar between the study arms, despite higher total drug exposure in patients randomized to quizartinib. The most frequent grade 3 or greater TEAEs in each arm were infections and cytopenia-related events.

Two patients discontinued quizartinib due to QTcF prolongation. Grade 3 QTcF (greater than 500 ms) occurred in 3% of patients treated with quizartinib, but no grade 4 cases were seen.

The adverse event profile for patients who resumed quizartinib following HSCT was similar to that of patients who received the drug pretransplant.

The combination of standard chemotherapy, with or without quizartinib, is currently being explored in the phase 3 QuANTUM-First trial, Dr. Cortes said.

Daiichi Sankyo sponsored the trial. Dr. Cortes reported financial relationships with Daiichi Sankyo, Pfizer, Arog, Astellas Pharma, and Novartis.

SOURCE: Cortes JE et al. ASH 2018, Abstract 563.

SAN DIEGO – Switching to lenalidomide maintenance after nine cycles of lenalidomide/dexamethasone (Rd) may avoid toxicity without sacrificing survival benefit in elderly multiple myeloma patients of intermediate fitness, results from a randomized trial showed.

Andrew D. Bowser/MDedge News

The Rd-R strategy yielded a “slight improvement” in event-free survival due largely to fewer adverse events, and no significant differences in progression-free or overall survival versus continuous Rd, reported Alessandra Larocca, MD, of GIMEMA/European Myeloma Network in Italy.

That finding suggests the promise of adapting myeloma treatment to a patient’s level of frailty or fitness, as determined by a myeloma frailty score, Dr. Larocca said at the annual meeting of the American Society of Hematology.

“A frailty-adjusted treatment approach is important in intermediate-fit patients to balance efficacy and safety,” she said.

The frailty score, developed by the International Myeloma Working Group (IMWG), classifies individuals as fit, intermediate, or frail based on age, comorbidities, cognitive status, and functional status. In a 2015 report in Blood, the IMWG frailty score was shown to predict mortality and treatment-related toxicity in elderly myeloma patients.

Dr. Larocca described results of the RV-MM-PI-0752 phase 3 study, which enrolled 199 newly diagnosed myeloma patients of intermediate fitness and randomized them to continuous Rd or nine cycles of Rd induction followed by lenalidomide maintenance (Rd-R).

The goal was to see if Rd could be “further optimized” for elderly, intermediate-fit patients, Dr. Larocca said.

The primary endpoint of RV-MM-PI-0752 was event-free survival, which included grade 4 hematologic and grade 3-4 nonhematologic adverse events, lenalidomide discontinuation, disease progression, or death.

Median event-free survival was 9.3 months for the Rd-R strategy, compared with 6.6 months for continuous Rd (hazard ratio, 0.72; 95% confidence interval, 0.52-0.99; P = .044), Dr. Larocca reported.

No difference was seen in survival outcomes, she added. The 20-month progression-free survival was 43% and 42% for Rd-R and continuous Rd, respectively. The 20-month overall survival was 84% vs. 79%, with P values that were not significant for either comparison.

Patients in the Rd-R group had a somewhat higher incidence of grade 3 or greater neutropenia, but the continuous Rd group had a somewhat higher rate of nonhematologic adverse events, leading to slightly higher rates of lenalidomide discontinuation and dose reduction, Dr. Larocca said.

Overall, 9% of patients dropped out of the RV-MM-PI-0752 trial within the first 60 days, due mainly to toxicity, she added.

“We have to evaluate how to better prevent toxicity, potentially enabling patients to stay on therapy longer,” Dr. Larocca said. “Probably we have to evaluate, in prospective clinical trials, the role of up-front dose adjustment or dose reduction, and subsequent dose increase in a subgroup of patients.”

Dr. Larocca reported disclosures related to Celgene, Bristol-Myers Squibb, Janssen-Cilag, Takeda, and Amgen.

SOURCE: Larocca A, et al. ASH 2018, Abstract 305.

SAN DIEGO – Switching to lenalidomide maintenance after nine cycles of lenalidomide/dexamethasone (Rd) may avoid toxicity without sacrificing survival benefit in elderly multiple myeloma patients of intermediate fitness, results from a randomized trial showed.

Andrew D. Bowser/MDedge News

The Rd-R strategy yielded a “slight improvement” in event-free survival due largely to fewer adverse events, and no significant differences in progression-free or overall survival versus continuous Rd, reported Alessandra Larocca, MD, of GIMEMA/European Myeloma Network in Italy.

That finding suggests the promise of adapting myeloma treatment to a patient’s level of frailty or fitness, as determined by a myeloma frailty score, Dr. Larocca said at the annual meeting of the American Society of Hematology.

“A frailty-adjusted treatment approach is important in intermediate-fit patients to balance efficacy and safety,” she said.

The frailty score, developed by the International Myeloma Working Group (IMWG), classifies individuals as fit, intermediate, or frail based on age, comorbidities, cognitive status, and functional status. In a 2015 report in Blood, the IMWG frailty score was shown to predict mortality and treatment-related toxicity in elderly myeloma patients.

Dr. Larocca described results of the RV-MM-PI-0752 phase 3 study, which enrolled 199 newly diagnosed myeloma patients of intermediate fitness and randomized them to continuous Rd or nine cycles of Rd induction followed by lenalidomide maintenance (Rd-R).

The goal was to see if Rd could be “further optimized” for elderly, intermediate-fit patients, Dr. Larocca said.

The primary endpoint of RV-MM-PI-0752 was event-free survival, which included grade 4 hematologic and grade 3-4 nonhematologic adverse events, lenalidomide discontinuation, disease progression, or death.

Median event-free survival was 9.3 months for the Rd-R strategy, compared with 6.6 months for continuous Rd (hazard ratio, 0.72; 95% confidence interval, 0.52-0.99; P = .044), Dr. Larocca reported.

No difference was seen in survival outcomes, she added. The 20-month progression-free survival was 43% and 42% for Rd-R and continuous Rd, respectively. The 20-month overall survival was 84% vs. 79%, with P values that were not significant for either comparison.

Patients in the Rd-R group had a somewhat higher incidence of grade 3 or greater neutropenia, but the continuous Rd group had a somewhat higher rate of nonhematologic adverse events, leading to slightly higher rates of lenalidomide discontinuation and dose reduction, Dr. Larocca said.

Overall, 9% of patients dropped out of the RV-MM-PI-0752 trial within the first 60 days, due mainly to toxicity, she added.

“We have to evaluate how to better prevent toxicity, potentially enabling patients to stay on therapy longer,” Dr. Larocca said. “Probably we have to evaluate, in prospective clinical trials, the role of up-front dose adjustment or dose reduction, and subsequent dose increase in a subgroup of patients.”

Dr. Larocca reported disclosures related to Celgene, Bristol-Myers Squibb, Janssen-Cilag, Takeda, and Amgen.

SOURCE: Larocca A, et al. ASH 2018, Abstract 305.

SAN DIEGO – Switching to lenalidomide maintenance after nine cycles of lenalidomide/dexamethasone (Rd) may avoid toxicity without sacrificing survival benefit in elderly multiple myeloma patients of intermediate fitness, results from a randomized trial showed.

Andrew D. Bowser/MDedge News

The Rd-R strategy yielded a “slight improvement” in event-free survival due largely to fewer adverse events, and no significant differences in progression-free or overall survival versus continuous Rd, reported Alessandra Larocca, MD, of GIMEMA/European Myeloma Network in Italy.

That finding suggests the promise of adapting myeloma treatment to a patient’s level of frailty or fitness, as determined by a myeloma frailty score, Dr. Larocca said at the annual meeting of the American Society of Hematology.

“A frailty-adjusted treatment approach is important in intermediate-fit patients to balance efficacy and safety,” she said.

The frailty score, developed by the International Myeloma Working Group (IMWG), classifies individuals as fit, intermediate, or frail based on age, comorbidities, cognitive status, and functional status. In a 2015 report in Blood, the IMWG frailty score was shown to predict mortality and treatment-related toxicity in elderly myeloma patients.

Dr. Larocca described results of the RV-MM-PI-0752 phase 3 study, which enrolled 199 newly diagnosed myeloma patients of intermediate fitness and randomized them to continuous Rd or nine cycles of Rd induction followed by lenalidomide maintenance (Rd-R).

The goal was to see if Rd could be “further optimized” for elderly, intermediate-fit patients, Dr. Larocca said.

The primary endpoint of RV-MM-PI-0752 was event-free survival, which included grade 4 hematologic and grade 3-4 nonhematologic adverse events, lenalidomide discontinuation, disease progression, or death.

Median event-free survival was 9.3 months for the Rd-R strategy, compared with 6.6 months for continuous Rd (hazard ratio, 0.72; 95% confidence interval, 0.52-0.99; P = .044), Dr. Larocca reported.

No difference was seen in survival outcomes, she added. The 20-month progression-free survival was 43% and 42% for Rd-R and continuous Rd, respectively. The 20-month overall survival was 84% vs. 79%, with P values that were not significant for either comparison.

Patients in the Rd-R group had a somewhat higher incidence of grade 3 or greater neutropenia, but the continuous Rd group had a somewhat higher rate of nonhematologic adverse events, leading to slightly higher rates of lenalidomide discontinuation and dose reduction, Dr. Larocca said.

Overall, 9% of patients dropped out of the RV-MM-PI-0752 trial within the first 60 days, due mainly to toxicity, she added.

“We have to evaluate how to better prevent toxicity, potentially enabling patients to stay on therapy longer,” Dr. Larocca said. “Probably we have to evaluate, in prospective clinical trials, the role of up-front dose adjustment or dose reduction, and subsequent dose increase in a subgroup of patients.”

Dr. Larocca reported disclosures related to Celgene, Bristol-Myers Squibb, Janssen-Cilag, Takeda, and Amgen.

SOURCE: Larocca A, et al. ASH 2018, Abstract 305.

SAN DIEGO – Nivolumab plus brentuximab vedotin may be a new treatment option for patients with relapsed/refractory primary mediastinal large B-cell lymphoma (PMBCL), according to investigators from the CheckMate 436 trial.

Interim results from this phase 1/2 trial revealed an overall response rate of 70%, including a complete response rate of 27%.

“It’s very promising ... to see this level of activity in this advanced, relapsed/refractory population,” said Joseph E. Eid, MD, senior vice president of Bristol-Myers Squibb, which is sponsoring CheckMate 436 in collaboration with Seattle Genetics.

Dr. Eid noted that adverse events (AEs) observed with this regimen were consistent with the safety profiles of nivolumab and brentuximab vedotin alone.

These results were presented as a poster at the annual meeting of the American Society of Hematology.

Dr. Eid noted that patients with relapsed or refractory PMBCL have limited treatment options.

“The initial therapy works well in 70% to 80% of patients but the patients who fail don’t have good options,” he said.

Prior research has shown that PMBCL is often characterized by overexpression of the PD-1 ligands PD-L1 and PD-L2, and most PMBCL expresses CD30.

Dr. Eid said CheckMate 436 (NCT02581631) was designed to “take advantage” of these characteristics by employing the anti-PD-1 checkpoint inhibitor nivolumab and the anti-CD30 antibody-drug conjugate brentuximab vedotin.

The interim analysis of this trial included 30 patients with relapsed/refractory PMBCL. Their median age at enrollment was 35.5 and 57% of patients were female. More than half of the patients (60%) had refractory disease, 23% had relapsed disease, and 17% had both.

The median number of prior therapies was two and 13% of patients had prior autologous stem cell transplant.

The patients received nivolumab at 240 mg and brentuximab vedotin at 1.8 mg/kg every 3 weeks until progression or unacceptable toxicity.

At a median follow-up of 6.1 months, 10 patients were still on treatment. Reasons for discontinuation included maximum clinical benefit, disease progression, AEs unrelated to treatment, patient request, and other concerns.

The rate of treatment-related AEs was 83%. The most common of these were neutropenia (27%), peripheral neuropathy (20%), hyperthyroidism (13%), rash (10%), and thrombocytopenia (10%).

Grade 3-4 treatment-related AEs included neutropenia (27%), thrombocytopenia (7%), decreased neutrophil count (7%), hypersensitivity (3%), diarrhea (3%), and maculopapular rash (3%).

The rate of serious treatment-related AEs was 10%. This included grade 3-4 diarrhea and maculopapular rash and grade 5 acute kidney injury.

The acute kidney injury was the only fatal AE considered treatment related. There were three other deaths in the trial, but they were considered unrelated to treatment.

The complete response rate was 27% (n = 8), and the partial response rate was 43% (n = 13), for an overall response rate of 70% (n = 21).

“The early indication is that 70% response is a pretty good outcome in a relapsed/refractory population that, otherwise, their outcome is pretty dismal,” Dr. Eid said.

Ten percent of patients (n = 3) had stable disease, 13% (n = 4) progressed, and investigators were unable to determine the status for 7% of patients (n = 2).

The median time to response was 1.3 months, and the median time to complete response was 3.0 months. The median duration of response and complete response were not reached.

Overall and progression-free survival data are not yet mature.

Still, the investigators concluded that nivolumab and brentuximab vedotin “may provide a new treatment option” for patients with relapsed/refractory PMBCL.

This trial is supported by Bristol-Myers Squibb in collaboration with Seattle Genetics. Investigators reported relationships with Bristol-Myers Squibb, Seattle Genetics, and a range of other companies.

[email protected]

SOURCE: Moskowitz AJ et al. ASH 2018. Abstract 1691.

SAN DIEGO – Nivolumab plus brentuximab vedotin may be a new treatment option for patients with relapsed/refractory primary mediastinal large B-cell lymphoma (PMBCL), according to investigators from the CheckMate 436 trial.

Interim results from this phase 1/2 trial revealed an overall response rate of 70%, including a complete response rate of 27%.

“It’s very promising ... to see this level of activity in this advanced, relapsed/refractory population,” said Joseph E. Eid, MD, senior vice president of Bristol-Myers Squibb, which is sponsoring CheckMate 436 in collaboration with Seattle Genetics.

Dr. Eid noted that adverse events (AEs) observed with this regimen were consistent with the safety profiles of nivolumab and brentuximab vedotin alone.

These results were presented as a poster at the annual meeting of the American Society of Hematology.

Dr. Eid noted that patients with relapsed or refractory PMBCL have limited treatment options.

“The initial therapy works well in 70% to 80% of patients but the patients who fail don’t have good options,” he said.

Prior research has shown that PMBCL is often characterized by overexpression of the PD-1 ligands PD-L1 and PD-L2, and most PMBCL expresses CD30.

Dr. Eid said CheckMate 436 (NCT02581631) was designed to “take advantage” of these characteristics by employing the anti-PD-1 checkpoint inhibitor nivolumab and the anti-CD30 antibody-drug conjugate brentuximab vedotin.

The interim analysis of this trial included 30 patients with relapsed/refractory PMBCL. Their median age at enrollment was 35.5 and 57% of patients were female. More than half of the patients (60%) had refractory disease, 23% had relapsed disease, and 17% had both.

The median number of prior therapies was two and 13% of patients had prior autologous stem cell transplant.

The patients received nivolumab at 240 mg and brentuximab vedotin at 1.8 mg/kg every 3 weeks until progression or unacceptable toxicity.

At a median follow-up of 6.1 months, 10 patients were still on treatment. Reasons for discontinuation included maximum clinical benefit, disease progression, AEs unrelated to treatment, patient request, and other concerns.

The rate of treatment-related AEs was 83%. The most common of these were neutropenia (27%), peripheral neuropathy (20%), hyperthyroidism (13%), rash (10%), and thrombocytopenia (10%).

Grade 3-4 treatment-related AEs included neutropenia (27%), thrombocytopenia (7%), decreased neutrophil count (7%), hypersensitivity (3%), diarrhea (3%), and maculopapular rash (3%).

The rate of serious treatment-related AEs was 10%. This included grade 3-4 diarrhea and maculopapular rash and grade 5 acute kidney injury.

The acute kidney injury was the only fatal AE considered treatment related. There were three other deaths in the trial, but they were considered unrelated to treatment.

The complete response rate was 27% (n = 8), and the partial response rate was 43% (n = 13), for an overall response rate of 70% (n = 21).

“The early indication is that 70% response is a pretty good outcome in a relapsed/refractory population that, otherwise, their outcome is pretty dismal,” Dr. Eid said.

Ten percent of patients (n = 3) had stable disease, 13% (n = 4) progressed, and investigators were unable to determine the status for 7% of patients (n = 2).

The median time to response was 1.3 months, and the median time to complete response was 3.0 months. The median duration of response and complete response were not reached.

Overall and progression-free survival data are not yet mature.

Still, the investigators concluded that nivolumab and brentuximab vedotin “may provide a new treatment option” for patients with relapsed/refractory PMBCL.

This trial is supported by Bristol-Myers Squibb in collaboration with Seattle Genetics. Investigators reported relationships with Bristol-Myers Squibb, Seattle Genetics, and a range of other companies.

[email protected]

SOURCE: Moskowitz AJ et al. ASH 2018. Abstract 1691.

SAN DIEGO – Nivolumab plus brentuximab vedotin may be a new treatment option for patients with relapsed/refractory primary mediastinal large B-cell lymphoma (PMBCL), according to investigators from the CheckMate 436 trial.

Interim results from this phase 1/2 trial revealed an overall response rate of 70%, including a complete response rate of 27%.

“It’s very promising ... to see this level of activity in this advanced, relapsed/refractory population,” said Joseph E. Eid, MD, senior vice president of Bristol-Myers Squibb, which is sponsoring CheckMate 436 in collaboration with Seattle Genetics.

Dr. Eid noted that adverse events (AEs) observed with this regimen were consistent with the safety profiles of nivolumab and brentuximab vedotin alone.

These results were presented as a poster at the annual meeting of the American Society of Hematology.

Dr. Eid noted that patients with relapsed or refractory PMBCL have limited treatment options.

“The initial therapy works well in 70% to 80% of patients but the patients who fail don’t have good options,” he said.

Prior research has shown that PMBCL is often characterized by overexpression of the PD-1 ligands PD-L1 and PD-L2, and most PMBCL expresses CD30.

Dr. Eid said CheckMate 436 (NCT02581631) was designed to “take advantage” of these characteristics by employing the anti-PD-1 checkpoint inhibitor nivolumab and the anti-CD30 antibody-drug conjugate brentuximab vedotin.

The interim analysis of this trial included 30 patients with relapsed/refractory PMBCL. Their median age at enrollment was 35.5 and 57% of patients were female. More than half of the patients (60%) had refractory disease, 23% had relapsed disease, and 17% had both.

The median number of prior therapies was two and 13% of patients had prior autologous stem cell transplant.

The patients received nivolumab at 240 mg and brentuximab vedotin at 1.8 mg/kg every 3 weeks until progression or unacceptable toxicity.

At a median follow-up of 6.1 months, 10 patients were still on treatment. Reasons for discontinuation included maximum clinical benefit, disease progression, AEs unrelated to treatment, patient request, and other concerns.

The rate of treatment-related AEs was 83%. The most common of these were neutropenia (27%), peripheral neuropathy (20%), hyperthyroidism (13%), rash (10%), and thrombocytopenia (10%).

Grade 3-4 treatment-related AEs included neutropenia (27%), thrombocytopenia (7%), decreased neutrophil count (7%), hypersensitivity (3%), diarrhea (3%), and maculopapular rash (3%).

The rate of serious treatment-related AEs was 10%. This included grade 3-4 diarrhea and maculopapular rash and grade 5 acute kidney injury.

The acute kidney injury was the only fatal AE considered treatment related. There were three other deaths in the trial, but they were considered unrelated to treatment.

The complete response rate was 27% (n = 8), and the partial response rate was 43% (n = 13), for an overall response rate of 70% (n = 21).

“The early indication is that 70% response is a pretty good outcome in a relapsed/refractory population that, otherwise, their outcome is pretty dismal,” Dr. Eid said.

Ten percent of patients (n = 3) had stable disease, 13% (n = 4) progressed, and investigators were unable to determine the status for 7% of patients (n = 2).

The median time to response was 1.3 months, and the median time to complete response was 3.0 months. The median duration of response and complete response were not reached.

Overall and progression-free survival data are not yet mature.

Still, the investigators concluded that nivolumab and brentuximab vedotin “may provide a new treatment option” for patients with relapsed/refractory PMBCL.

This trial is supported by Bristol-Myers Squibb in collaboration with Seattle Genetics. Investigators reported relationships with Bristol-Myers Squibb, Seattle Genetics, and a range of other companies.

[email protected]

SOURCE: Moskowitz AJ et al. ASH 2018. Abstract 1691.

SAN DIEGO – The success or failure of hematopoietic cell transplants may be related to the diversity of species in the gut microbiome, investigators contend.

Neil Osterweil/MDedge News

A study of fecal samples from patients scheduled to undergo hematopoietic cell transplant (HCT) in the United States, Europe, and Japan showed that intestinal microbial diversity was significantly associated with overall survival, reported Jonathan U. Peled, MD, PhD, from the bone marrow transplantation service at Memorial Sloan Kettering Cancer Center in New York City.

“Patients with low diversity pretransplant have a poorer overall survival than patients with a higher diversity after transplantation,” he said at the annual meeting of the American Society of Hematology. “The implication is, if we could come up with a way to remediate microbiome injury, there might be time to implement it before the transplant.”

There are about 100 trillion symbiotic microbes in and on the human body, and 95% of them live in the gastrointestinal tract, which has a surface area that if stretched out would equal the size of two tennis courts, Dr. Peled said.

Previous studies by his group and others have shown that the composition of intestinal microbiota is associated with survival, relapses, graft-versus-host disease, and infections in patients in the early weeks after allogeneic HCT.

The international team previously reported that intestinal diversity measured around the time of neutrophil engraftment was predictive of overall survival, and they hypothesized that the same might be true of the pretransplant microbiota composition.

To test this idea, they collected 1,922 stools samples approximately once weekly for 3 weeks pretransplant from 991 adult patients scheduled for allo-HCT for various diagnoses in two U.S. cohorts and one cohort each in Europe and Japan.

They found that on average patients in all four cohorts had microbiota diversity values ranging from 70% to 150% lower than those of healthy volunteers whose samples were sequenced by the investigators, as well as those in a publicly available database.

The investigators also asked whether one or more bacterial species accounted for 30% or more of a microbiome, a phenomenon known as “monodomination.”

“A third, or in some cases 95+%, of bacteria in an individual’s intestine are all the exact same strain,” Dr. Peled said.

They found that the incidence and prevalence of the monodomination phenotype was “strikingly similar” at all four transplant sites.


The patterns of microbiota injury were similar despite differences in antibiotic strategies among the four centers and different dietary patterns of patients in the regions studied.

Studies in animal models suggest that T cells responsible for graft-versus-host disease migrate to the gut as early as 2 or 3 days post transplant, and by that time more than half of transplant patients have a monodomination event in their guts, Dr. Peled said.

Some strategies to remediate or prevent microbiome damage – and potentially improve HCT outcomes – may include the use of over-the-counter or custom-made probiotics, fecal transplants, a “prebiotic” approach in which the patient is asked to follow a specific diet that promotes the growth of beneficial bacteria, or a “postbiotic” approach in which patients receive metabolites of agents or foods thought to have a beneficial effect.

“Finally, we can think about different antibiotic strategies, to use or not use different types of antibiotics at different times in a rational way,” Dr. Peled said.

Dr. Peled reported current or prior financial relationships with Seres Therapeutics, the Parker Institute for Cancer Immunotherapy, and Merck/Society for Immunotherapy of Cancer.

SOURCE: Peled JU et al. ASH 2018, Abstract 811.

SAN DIEGO – The success or failure of hematopoietic cell transplants may be related to the diversity of species in the gut microbiome, investigators contend.

Neil Osterweil/MDedge News

A study of fecal samples from patients scheduled to undergo hematopoietic cell transplant (HCT) in the United States, Europe, and Japan showed that intestinal microbial diversity was significantly associated with overall survival, reported Jonathan U. Peled, MD, PhD, from the bone marrow transplantation service at Memorial Sloan Kettering Cancer Center in New York City.

“Patients with low diversity pretransplant have a poorer overall survival than patients with a higher diversity after transplantation,” he said at the annual meeting of the American Society of Hematology. “The implication is, if we could come up with a way to remediate microbiome injury, there might be time to implement it before the transplant.”

There are about 100 trillion symbiotic microbes in and on the human body, and 95% of them live in the gastrointestinal tract, which has a surface area that if stretched out would equal the size of two tennis courts, Dr. Peled said.

Previous studies by his group and others have shown that the composition of intestinal microbiota is associated with survival, relapses, graft-versus-host disease, and infections in patients in the early weeks after allogeneic HCT.

The international team previously reported that intestinal diversity measured around the time of neutrophil engraftment was predictive of overall survival, and they hypothesized that the same might be true of the pretransplant microbiota composition.

To test this idea, they collected 1,922 stools samples approximately once weekly for 3 weeks pretransplant from 991 adult patients scheduled for allo-HCT for various diagnoses in two U.S. cohorts and one cohort each in Europe and Japan.

They found that on average patients in all four cohorts had microbiota diversity values ranging from 70% to 150% lower than those of healthy volunteers whose samples were sequenced by the investigators, as well as those in a publicly available database.

The investigators also asked whether one or more bacterial species accounted for 30% or more of a microbiome, a phenomenon known as “monodomination.”

“A third, or in some cases 95+%, of bacteria in an individual’s intestine are all the exact same strain,” Dr. Peled said.

They found that the incidence and prevalence of the monodomination phenotype was “strikingly similar” at all four transplant sites.


The patterns of microbiota injury were similar despite differences in antibiotic strategies among the four centers and different dietary patterns of patients in the regions studied.

Studies in animal models suggest that T cells responsible for graft-versus-host disease migrate to the gut as early as 2 or 3 days post transplant, and by that time more than half of transplant patients have a monodomination event in their guts, Dr. Peled said.

Some strategies to remediate or prevent microbiome damage – and potentially improve HCT outcomes – may include the use of over-the-counter or custom-made probiotics, fecal transplants, a “prebiotic” approach in which the patient is asked to follow a specific diet that promotes the growth of beneficial bacteria, or a “postbiotic” approach in which patients receive metabolites of agents or foods thought to have a beneficial effect.

“Finally, we can think about different antibiotic strategies, to use or not use different types of antibiotics at different times in a rational way,” Dr. Peled said.

Dr. Peled reported current or prior financial relationships with Seres Therapeutics, the Parker Institute for Cancer Immunotherapy, and Merck/Society for Immunotherapy of Cancer.

SOURCE: Peled JU et al. ASH 2018, Abstract 811.

SAN DIEGO – The success or failure of hematopoietic cell transplants may be related to the diversity of species in the gut microbiome, investigators contend.

Neil Osterweil/MDedge News

A study of fecal samples from patients scheduled to undergo hematopoietic cell transplant (HCT) in the United States, Europe, and Japan showed that intestinal microbial diversity was significantly associated with overall survival, reported Jonathan U. Peled, MD, PhD, from the bone marrow transplantation service at Memorial Sloan Kettering Cancer Center in New York City.

“Patients with low diversity pretransplant have a poorer overall survival than patients with a higher diversity after transplantation,” he said at the annual meeting of the American Society of Hematology. “The implication is, if we could come up with a way to remediate microbiome injury, there might be time to implement it before the transplant.”

There are about 100 trillion symbiotic microbes in and on the human body, and 95% of them live in the gastrointestinal tract, which has a surface area that if stretched out would equal the size of two tennis courts, Dr. Peled said.

Previous studies by his group and others have shown that the composition of intestinal microbiota is associated with survival, relapses, graft-versus-host disease, and infections in patients in the early weeks after allogeneic HCT.

The international team previously reported that intestinal diversity measured around the time of neutrophil engraftment was predictive of overall survival, and they hypothesized that the same might be true of the pretransplant microbiota composition.

To test this idea, they collected 1,922 stools samples approximately once weekly for 3 weeks pretransplant from 991 adult patients scheduled for allo-HCT for various diagnoses in two U.S. cohorts and one cohort each in Europe and Japan.

They found that on average patients in all four cohorts had microbiota diversity values ranging from 70% to 150% lower than those of healthy volunteers whose samples were sequenced by the investigators, as well as those in a publicly available database.

The investigators also asked whether one or more bacterial species accounted for 30% or more of a microbiome, a phenomenon known as “monodomination.”

“A third, or in some cases 95+%, of bacteria in an individual’s intestine are all the exact same strain,” Dr. Peled said.

They found that the incidence and prevalence of the monodomination phenotype was “strikingly similar” at all four transplant sites.


The patterns of microbiota injury were similar despite differences in antibiotic strategies among the four centers and different dietary patterns of patients in the regions studied.

Studies in animal models suggest that T cells responsible for graft-versus-host disease migrate to the gut as early as 2 or 3 days post transplant, and by that time more than half of transplant patients have a monodomination event in their guts, Dr. Peled said.

Some strategies to remediate or prevent microbiome damage – and potentially improve HCT outcomes – may include the use of over-the-counter or custom-made probiotics, fecal transplants, a “prebiotic” approach in which the patient is asked to follow a specific diet that promotes the growth of beneficial bacteria, or a “postbiotic” approach in which patients receive metabolites of agents or foods thought to have a beneficial effect.

“Finally, we can think about different antibiotic strategies, to use or not use different types of antibiotics at different times in a rational way,” Dr. Peled said.

Dr. Peled reported current or prior financial relationships with Seres Therapeutics, the Parker Institute for Cancer Immunotherapy, and Merck/Society for Immunotherapy of Cancer.

SOURCE: Peled JU et al. ASH 2018, Abstract 811.

SAN DIEGO – A newly approved treatment regimen provides a survival benefit over standard therapy for patients with CD30-positive peripheral T-cell lymphomas (PTCLs), according to new research presented at the annual meeting of the American Society of Hematology.

In the ECHELON-2 trial, patients who received brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin, and prednisone (CHP) had superior progression-free survival (PFS) and overall survival (OS), compared with patients who received standard treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).

These results supported the recent U.S. approval of BV in combination with CHP for adults with previously untreated, systemic anaplastic large cell lymphoma or other CD30-expressing PTCLs.

“ECHELON-2 is the first prospective trial in peripheral T-cell lymphoma to show an overall survival benefit over CHOP,” said Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer Center, with locations in New York and New Jersey.

Dr. Horwitz presented data from this trial at the ASH meeting. Results were simultaneously published in the Lancet (2018 Dec 3. doi: 10.1016/S0140-6736[18]32984-2).

ECHELON-2 (NCT01777152) enrolled 452 patients with previously untreated, CD30-positive PTCL. Subtypes included ALK-positive or ALK-negative systemic anaplastic large-cell lymphoma, PTCL not otherwise specified, angioimmunoblastic T-cell lymphoma, enteropathy-associated T-cell lymphoma, and adult T-cell leukemia/lymphoma.

Patients were randomized to receive BV-CHP plus placebo (n = 226) or CHOP plus placebo (n = 226) every 3 weeks for six to eight cycles.

At baseline, the median age was 58 in the BV-CHP arm and the CHOP arm. The majority of patients were male – 59% in the BV-CHP arm and 67% in the CHOP arm – and most patients had stage III/IV disease, 81% and 80%, respectively.

In all, 89% of patients in the BV-CHP arm and 81% in the CHOP arm completed six or more cycles of their assigned treatment.

The overall response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P = .0032). The complete response rates were 68% and 56%, respectively (P = .0066).

At a median follow-up of 36.2 months, the median PFS was 48.2 months in the BV-CHP arm and 20.8 months in the CHOP arm. The rate of death or progression was 42% in the BV-CHP arm and 55% in the CHOP arm (hazard ratio = 0.71, P = .011).

At a median follow-up of 42.1 months, the median OS was not reached in either treatment arm. The rate of death was 23% in the BV-CHP arm and 32% in the CHOP arm (HR = 0.66, P = .0244).

Dr. Horwitz noted that this study was not powered to determine differences in PFS or OS by PTCL subtypes.

BV-CHP had a safety profile comparable with that of CHOP, Dr. Horwitz said.

The rate of adverse events (AEs) was 99% in the BV-CHP arm and 98% in the CHOP arm. Grade 3 or higher AEs occurred in 66% and 65% of patients, respectively. Serious AEs occurred in 39% and 38%, respectively.

Three percent of patients in the BV-CHP arm and 4% of those in the CHOP arm had fatal AEs.

The study was funded by Seattle Genetics, Millennium Pharmaceuticals, and the National Institutes of Health. Dr. Horwitz reported relationships with Seattle Genetics, Millennium Pharmaceuticals, and other companies.

[email protected]

SOURCE: Horwitz S et al. ASH 2018, Abstract 997.

SAN DIEGO – A newly approved treatment regimen provides a survival benefit over standard therapy for patients with CD30-positive peripheral T-cell lymphomas (PTCLs), according to new research presented at the annual meeting of the American Society of Hematology.

In the ECHELON-2 trial, patients who received brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin, and prednisone (CHP) had superior progression-free survival (PFS) and overall survival (OS), compared with patients who received standard treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).

These results supported the recent U.S. approval of BV in combination with CHP for adults with previously untreated, systemic anaplastic large cell lymphoma or other CD30-expressing PTCLs.

“ECHELON-2 is the first prospective trial in peripheral T-cell lymphoma to show an overall survival benefit over CHOP,” said Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer Center, with locations in New York and New Jersey.

Dr. Horwitz presented data from this trial at the ASH meeting. Results were simultaneously published in the Lancet (2018 Dec 3. doi: 10.1016/S0140-6736[18]32984-2).

ECHELON-2 (NCT01777152) enrolled 452 patients with previously untreated, CD30-positive PTCL. Subtypes included ALK-positive or ALK-negative systemic anaplastic large-cell lymphoma, PTCL not otherwise specified, angioimmunoblastic T-cell lymphoma, enteropathy-associated T-cell lymphoma, and adult T-cell leukemia/lymphoma.

Patients were randomized to receive BV-CHP plus placebo (n = 226) or CHOP plus placebo (n = 226) every 3 weeks for six to eight cycles.

At baseline, the median age was 58 in the BV-CHP arm and the CHOP arm. The majority of patients were male – 59% in the BV-CHP arm and 67% in the CHOP arm – and most patients had stage III/IV disease, 81% and 80%, respectively.

In all, 89% of patients in the BV-CHP arm and 81% in the CHOP arm completed six or more cycles of their assigned treatment.

The overall response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P = .0032). The complete response rates were 68% and 56%, respectively (P = .0066).

At a median follow-up of 36.2 months, the median PFS was 48.2 months in the BV-CHP arm and 20.8 months in the CHOP arm. The rate of death or progression was 42% in the BV-CHP arm and 55% in the CHOP arm (hazard ratio = 0.71, P = .011).

At a median follow-up of 42.1 months, the median OS was not reached in either treatment arm. The rate of death was 23% in the BV-CHP arm and 32% in the CHOP arm (HR = 0.66, P = .0244).

Dr. Horwitz noted that this study was not powered to determine differences in PFS or OS by PTCL subtypes.

BV-CHP had a safety profile comparable with that of CHOP, Dr. Horwitz said.

The rate of adverse events (AEs) was 99% in the BV-CHP arm and 98% in the CHOP arm. Grade 3 or higher AEs occurred in 66% and 65% of patients, respectively. Serious AEs occurred in 39% and 38%, respectively.

Three percent of patients in the BV-CHP arm and 4% of those in the CHOP arm had fatal AEs.

The study was funded by Seattle Genetics, Millennium Pharmaceuticals, and the National Institutes of Health. Dr. Horwitz reported relationships with Seattle Genetics, Millennium Pharmaceuticals, and other companies.

[email protected]

SOURCE: Horwitz S et al. ASH 2018, Abstract 997.

SAN DIEGO – A newly approved treatment regimen provides a survival benefit over standard therapy for patients with CD30-positive peripheral T-cell lymphomas (PTCLs), according to new research presented at the annual meeting of the American Society of Hematology.

In the ECHELON-2 trial, patients who received brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin, and prednisone (CHP) had superior progression-free survival (PFS) and overall survival (OS), compared with patients who received standard treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).

These results supported the recent U.S. approval of BV in combination with CHP for adults with previously untreated, systemic anaplastic large cell lymphoma or other CD30-expressing PTCLs.

“ECHELON-2 is the first prospective trial in peripheral T-cell lymphoma to show an overall survival benefit over CHOP,” said Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer Center, with locations in New York and New Jersey.

Dr. Horwitz presented data from this trial at the ASH meeting. Results were simultaneously published in the Lancet (2018 Dec 3. doi: 10.1016/S0140-6736[18]32984-2).

ECHELON-2 (NCT01777152) enrolled 452 patients with previously untreated, CD30-positive PTCL. Subtypes included ALK-positive or ALK-negative systemic anaplastic large-cell lymphoma, PTCL not otherwise specified, angioimmunoblastic T-cell lymphoma, enteropathy-associated T-cell lymphoma, and adult T-cell leukemia/lymphoma.

Patients were randomized to receive BV-CHP plus placebo (n = 226) or CHOP plus placebo (n = 226) every 3 weeks for six to eight cycles.

At baseline, the median age was 58 in the BV-CHP arm and the CHOP arm. The majority of patients were male – 59% in the BV-CHP arm and 67% in the CHOP arm – and most patients had stage III/IV disease, 81% and 80%, respectively.

In all, 89% of patients in the BV-CHP arm and 81% in the CHOP arm completed six or more cycles of their assigned treatment.

The overall response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P = .0032). The complete response rates were 68% and 56%, respectively (P = .0066).

At a median follow-up of 36.2 months, the median PFS was 48.2 months in the BV-CHP arm and 20.8 months in the CHOP arm. The rate of death or progression was 42% in the BV-CHP arm and 55% in the CHOP arm (hazard ratio = 0.71, P = .011).

At a median follow-up of 42.1 months, the median OS was not reached in either treatment arm. The rate of death was 23% in the BV-CHP arm and 32% in the CHOP arm (HR = 0.66, P = .0244).

Dr. Horwitz noted that this study was not powered to determine differences in PFS or OS by PTCL subtypes.

BV-CHP had a safety profile comparable with that of CHOP, Dr. Horwitz said.

The rate of adverse events (AEs) was 99% in the BV-CHP arm and 98% in the CHOP arm. Grade 3 or higher AEs occurred in 66% and 65% of patients, respectively. Serious AEs occurred in 39% and 38%, respectively.

Three percent of patients in the BV-CHP arm and 4% of those in the CHOP arm had fatal AEs.

The study was funded by Seattle Genetics, Millennium Pharmaceuticals, and the National Institutes of Health. Dr. Horwitz reported relationships with Seattle Genetics, Millennium Pharmaceuticals, and other companies.

[email protected]

SOURCE: Horwitz S et al. ASH 2018, Abstract 997.

SAN DIEGO – A novel human factor VIII variant shows promise for the treatment of severe hemophilia A, according to preliminary findings from the ongoing Gene Therapy for Hemophilia A (GO-8) phase 1/2 dose-escalation study.

Crystal/Wikimedia Commons/Creative Commons Attribution 2.0

A single peripheral vein infusion of the factor VIII (FVIII) variant resulted in FVIII activity levels of about 6% versus levels of no more than 1% of normal at study entry in the first four patients, Pratima Chowdary, MD, reported at the annual meeting of the American Society of Hematology.

The variant, known as scAAV2/8-LP1-hFIXco, is being investigated for safety and efficacy in the GO-8 investigator-led, open-label, nonrandomized trial at a low, mid, and high dose (2 x 10¹¹ vector genomes/kg, 6 x 10¹¹ vector genomes/kg, and 2 x 10¹² vector genomes/kg), said Dr. Chowdary, a consultant hematologist at Royal Free Hospital London.

The main study period is 6 months and 15 years of follow-up are offered.

The first patient received the low dose and achieved FVIII of about 6% within 1 week. That level persisted for about 6 weeks when the patient developed a transaminitis, which promptly responded to steroids.

His steady-state FVIII within a few weeks was 7% by one-stage assay and about 3% by chromogenic assay, Dr. Chowdary said.

The remaining patients received the mid dose and also achieved FVIII levels of about 6% within a week. Patient 2 started on prophylactic steroids at week 6, per protocol, and did not experience transaminitis, but also had no increase in FVIII level, compared with the low-dose patient, which may be explained by the potential drug half-life, she noted.

Patient 3 reached a FVIII level of about 30% by week 4. He developed transaminitis at that time, which was about 2 weeks before planned prophylactic drug administration, but the transaminitis was controlled by steroids over a period of about 8-10 weeks.

“His steady-state FVIII level by one stage was 34% and by chromogenic assay was 17%. He has not had any bleeds since his gene transfer and has not required any FVIII concentrate either,” she said.

Patient 4 reached a FVIII level of about 40% by week 4. He was given prophylactic steroids at that time because of the occurrence of transaminitis at week 4 in Patient 3.

The patient developed transaminitis during steroid taper about 4 weeks later, perhaps because of the rapid taper, Dr. Chowdary said, adding that the transaminitis was well controlled with steroids, but follow-up in this patient has only been about 12 weeks.

“The characteristics of FVIII expression in this patient are very similar to the previous patient. ... We suspect he will have a steady-state level of about 30%,” she said. “Again, he’s had no bleeds since his gene transfer and has not required any FVIII concentrate.”

The single infusion of this novel vector was well tolerated in each patient, with no evidence of infusion-related reactions, neutralizing anti-FVIII antibodies, or vector-related adverse events.

“The transgene expression was achieved in all patients and at both vector dosages,” Dr. Chowdary said. “What is very important is that the levels of less than 10% had only a modest impact on the bleed rates and FVIII usage, whereas an expression of more than 10% resulted in zero bleeds and the patient did not require any additional FVIII treatment.”

The data are “encouraging,” she said. “We look forward to escalating the dose in the next patient.”

Dr. Chowdary reported financial relationships with Bayer, CSL Behring, Baxalta, Baxter, Biogen, Freeline, Novo Nordisk, Pfizer, Roche, Shire, and SOBI.

[email protected]

SOURCE: Chowdary P et al. ASH 2018, Abstract 489.

SAN DIEGO – A novel human factor VIII variant shows promise for the treatment of severe hemophilia A, according to preliminary findings from the ongoing Gene Therapy for Hemophilia A (GO-8) phase 1/2 dose-escalation study.

Crystal/Wikimedia Commons/Creative Commons Attribution 2.0

A single peripheral vein infusion of the factor VIII (FVIII) variant resulted in FVIII activity levels of about 6% versus levels of no more than 1% of normal at study entry in the first four patients, Pratima Chowdary, MD, reported at the annual meeting of the American Society of Hematology.

The variant, known as scAAV2/8-LP1-hFIXco, is being investigated for safety and efficacy in the GO-8 investigator-led, open-label, nonrandomized trial at a low, mid, and high dose (2 x 10¹¹ vector genomes/kg, 6 x 10¹¹ vector genomes/kg, and 2 x 10¹² vector genomes/kg), said Dr. Chowdary, a consultant hematologist at Royal Free Hospital London.

The main study period is 6 months and 15 years of follow-up are offered.

The first patient received the low dose and achieved FVIII of about 6% within 1 week. That level persisted for about 6 weeks when the patient developed a transaminitis, which promptly responded to steroids.

His steady-state FVIII within a few weeks was 7% by one-stage assay and about 3% by chromogenic assay, Dr. Chowdary said.

The remaining patients received the mid dose and also achieved FVIII levels of about 6% within a week. Patient 2 started on prophylactic steroids at week 6, per protocol, and did not experience transaminitis, but also had no increase in FVIII level, compared with the low-dose patient, which may be explained by the potential drug half-life, she noted.

Patient 3 reached a FVIII level of about 30% by week 4. He developed transaminitis at that time, which was about 2 weeks before planned prophylactic drug administration, but the transaminitis was controlled by steroids over a period of about 8-10 weeks.

“His steady-state FVIII level by one stage was 34% and by chromogenic assay was 17%. He has not had any bleeds since his gene transfer and has not required any FVIII concentrate either,” she said.

Patient 4 reached a FVIII level of about 40% by week 4. He was given prophylactic steroids at that time because of the occurrence of transaminitis at week 4 in Patient 3.

The patient developed transaminitis during steroid taper about 4 weeks later, perhaps because of the rapid taper, Dr. Chowdary said, adding that the transaminitis was well controlled with steroids, but follow-up in this patient has only been about 12 weeks.

“The characteristics of FVIII expression in this patient are very similar to the previous patient. ... We suspect he will have a steady-state level of about 30%,” she said. “Again, he’s had no bleeds since his gene transfer and has not required any FVIII concentrate.”

The single infusion of this novel vector was well tolerated in each patient, with no evidence of infusion-related reactions, neutralizing anti-FVIII antibodies, or vector-related adverse events.

“The transgene expression was achieved in all patients and at both vector dosages,” Dr. Chowdary said. “What is very important is that the levels of less than 10% had only a modest impact on the bleed rates and FVIII usage, whereas an expression of more than 10% resulted in zero bleeds and the patient did not require any additional FVIII treatment.”

The data are “encouraging,” she said. “We look forward to escalating the dose in the next patient.”

Dr. Chowdary reported financial relationships with Bayer, CSL Behring, Baxalta, Baxter, Biogen, Freeline, Novo Nordisk, Pfizer, Roche, Shire, and SOBI.

[email protected]

SOURCE: Chowdary P et al. ASH 2018, Abstract 489.

SAN DIEGO – A novel human factor VIII variant shows promise for the treatment of severe hemophilia A, according to preliminary findings from the ongoing Gene Therapy for Hemophilia A (GO-8) phase 1/2 dose-escalation study.

Crystal/Wikimedia Commons/Creative Commons Attribution 2.0

A single peripheral vein infusion of the factor VIII (FVIII) variant resulted in FVIII activity levels of about 6% versus levels of no more than 1% of normal at study entry in the first four patients, Pratima Chowdary, MD, reported at the annual meeting of the American Society of Hematology.

The variant, known as scAAV2/8-LP1-hFIXco, is being investigated for safety and efficacy in the GO-8 investigator-led, open-label, nonrandomized trial at a low, mid, and high dose (2 x 10¹¹ vector genomes/kg, 6 x 10¹¹ vector genomes/kg, and 2 x 10¹² vector genomes/kg), said Dr. Chowdary, a consultant hematologist at Royal Free Hospital London.

The main study period is 6 months and 15 years of follow-up are offered.

The first patient received the low dose and achieved FVIII of about 6% within 1 week. That level persisted for about 6 weeks when the patient developed a transaminitis, which promptly responded to steroids.

His steady-state FVIII within a few weeks was 7% by one-stage assay and about 3% by chromogenic assay, Dr. Chowdary said.

The remaining patients received the mid dose and also achieved FVIII levels of about 6% within a week. Patient 2 started on prophylactic steroids at week 6, per protocol, and did not experience transaminitis, but also had no increase in FVIII level, compared with the low-dose patient, which may be explained by the potential drug half-life, she noted.

Patient 3 reached a FVIII level of about 30% by week 4. He developed transaminitis at that time, which was about 2 weeks before planned prophylactic drug administration, but the transaminitis was controlled by steroids over a period of about 8-10 weeks.

“His steady-state FVIII level by one stage was 34% and by chromogenic assay was 17%. He has not had any bleeds since his gene transfer and has not required any FVIII concentrate either,” she said.

Patient 4 reached a FVIII level of about 40% by week 4. He was given prophylactic steroids at that time because of the occurrence of transaminitis at week 4 in Patient 3.

The patient developed transaminitis during steroid taper about 4 weeks later, perhaps because of the rapid taper, Dr. Chowdary said, adding that the transaminitis was well controlled with steroids, but follow-up in this patient has only been about 12 weeks.

“The characteristics of FVIII expression in this patient are very similar to the previous patient. ... We suspect he will have a steady-state level of about 30%,” she said. “Again, he’s had no bleeds since his gene transfer and has not required any FVIII concentrate.”

The single infusion of this novel vector was well tolerated in each patient, with no evidence of infusion-related reactions, neutralizing anti-FVIII antibodies, or vector-related adverse events.

“The transgene expression was achieved in all patients and at both vector dosages,” Dr. Chowdary said. “What is very important is that the levels of less than 10% had only a modest impact on the bleed rates and FVIII usage, whereas an expression of more than 10% resulted in zero bleeds and the patient did not require any additional FVIII treatment.”

The data are “encouraging,” she said. “We look forward to escalating the dose in the next patient.”

Dr. Chowdary reported financial relationships with Bayer, CSL Behring, Baxalta, Baxter, Biogen, Freeline, Novo Nordisk, Pfizer, Roche, Shire, and SOBI.

[email protected]

SOURCE: Chowdary P et al. ASH 2018, Abstract 489.

SAN DIEGO – When it comes to aggressive care at the end of life, hematologists stand alone.

Hematology patients are more likely than are other patients to undergo chemotherapy and visit emergency departments and intensive care units when they’re near death, and they’re less likely to be referred for palliative care, according to David Hui, MD, an oncologist and palliative care specialist at the MD Anderson Cancer Center in Houston.

An analysis at the center, for example, found that 43% of hematology cancer patients received chemotherapy within the last 30 days of life, compared with 14% of patients with solid tumors.

“That’s not a number we’re proud of,” Dr. Hui said at the annual meeting of the American Society of Hematology. “Ultimately, at the end of life, do we want our patients to be in this setting? There is room for improvement.”

The cancer center isn’t an outlier on this front, Dr. Hui said. Data from other institutions in the United States and internationally confirm that hematologic oncologists tend to provide more aggressive care at the end of a patient’s life, compared with other cancer specialists.

“If you’re one of those patients, this is a very big deal,” said Dr. Hui, especially in light of data that suggest hematology patients get fewer referrals to palliative care than do other cancer patients. “Oncologists are optimistic, and hematologic oncologists especially,” he said.

Dr. Hui led a 2014 study of 816 adult cancer patients who died while under care at MD Anderson Cancer Center during 6 months in 2009 and 2010 (Cancer. 2014 May 15; 120[10]:1572-8).

“We found that patients with hematological malignancies were more likely to have multiple emergency room visits, intensive care unit admissions and death, and cancer treatments in the last weeks of life compared to patients with solid tumors,” the study authors wrote. “We also identified a relative lack of palliative care involvement in hematologic patients.”

Specifically, hematology cancer patients were much more likely to get aggressive end-of-life care than were the other cancer patients (odds ratio, 6.63, P less than .001).

Dr. Hui had led an earlier study that looked at the same 816 cancer patients and found that 45% had received palliative care consultations. But the researchers also found that patients with hematologic malignancies had significantly fewer palliative care referrals, the longest time between an advanced cancer diagnosis and a palliative care consultation, and one of the largest numbers of medical team encounters – a median of 38 – before palliative care (Oncologist. 2012;17[12]:1574-80).

In light of these numbers, policies at MD Anderson Cancer Center “are evolving rapidly,” Dr. Hui said.

He urged colleagues to think about the wishes of their patients. “What do patients really want? Good symptom control, time with family, not being a burden, not a prolonging dying process, having a sense of control during the middle of the turmoil.”

Dr. Hui added that the attitudes of oncologists regarding palliative care can affect whether patients get timely referrals to consultations. He led a 2016 study that surveyed 182 oncologists about end-of-life care and found that “many oncologists have a favorable attitude toward EOL care; this, in turn, was associated with greater provision of primary palliative care and higher rates of referral to specialist palliative care.”

However, “we found that hematologic oncology specialists expressed lower comfort levels compared with their solid tumor counterparts,” a finding that reflects the results of other studies, the study authors wrote (Oncologist. 2016 Sep;21[9]:1149-55).

The stigma surrounding palliative care is a sticking point, Dr. Hui said, and has sparked a “rebranding” effort. Negative feelings about palliative decrease when it’s called “supportive care,” he said, and the new term is being adopted worldwide.

Dr. Hui reported having no financial disclosures.

SAN DIEGO – When it comes to aggressive care at the end of life, hematologists stand alone.

Hematology patients are more likely than are other patients to undergo chemotherapy and visit emergency departments and intensive care units when they’re near death, and they’re less likely to be referred for palliative care, according to David Hui, MD, an oncologist and palliative care specialist at the MD Anderson Cancer Center in Houston.

An analysis at the center, for example, found that 43% of hematology cancer patients received chemotherapy within the last 30 days of life, compared with 14% of patients with solid tumors.

“That’s not a number we’re proud of,” Dr. Hui said at the annual meeting of the American Society of Hematology. “Ultimately, at the end of life, do we want our patients to be in this setting? There is room for improvement.”

The cancer center isn’t an outlier on this front, Dr. Hui said. Data from other institutions in the United States and internationally confirm that hematologic oncologists tend to provide more aggressive care at the end of a patient’s life, compared with other cancer specialists.

“If you’re one of those patients, this is a very big deal,” said Dr. Hui, especially in light of data that suggest hematology patients get fewer referrals to palliative care than do other cancer patients. “Oncologists are optimistic, and hematologic oncologists especially,” he said.

Dr. Hui led a 2014 study of 816 adult cancer patients who died while under care at MD Anderson Cancer Center during 6 months in 2009 and 2010 (Cancer. 2014 May 15; 120[10]:1572-8).

“We found that patients with hematological malignancies were more likely to have multiple emergency room visits, intensive care unit admissions and death, and cancer treatments in the last weeks of life compared to patients with solid tumors,” the study authors wrote. “We also identified a relative lack of palliative care involvement in hematologic patients.”

Specifically, hematology cancer patients were much more likely to get aggressive end-of-life care than were the other cancer patients (odds ratio, 6.63, P less than .001).

Dr. Hui had led an earlier study that looked at the same 816 cancer patients and found that 45% had received palliative care consultations. But the researchers also found that patients with hematologic malignancies had significantly fewer palliative care referrals, the longest time between an advanced cancer diagnosis and a palliative care consultation, and one of the largest numbers of medical team encounters – a median of 38 – before palliative care (Oncologist. 2012;17[12]:1574-80).

In light of these numbers, policies at MD Anderson Cancer Center “are evolving rapidly,” Dr. Hui said.

He urged colleagues to think about the wishes of their patients. “What do patients really want? Good symptom control, time with family, not being a burden, not a prolonging dying process, having a sense of control during the middle of the turmoil.”

Dr. Hui added that the attitudes of oncologists regarding palliative care can affect whether patients get timely referrals to consultations. He led a 2016 study that surveyed 182 oncologists about end-of-life care and found that “many oncologists have a favorable attitude toward EOL care; this, in turn, was associated with greater provision of primary palliative care and higher rates of referral to specialist palliative care.”

However, “we found that hematologic oncology specialists expressed lower comfort levels compared with their solid tumor counterparts,” a finding that reflects the results of other studies, the study authors wrote (Oncologist. 2016 Sep;21[9]:1149-55).

The stigma surrounding palliative care is a sticking point, Dr. Hui said, and has sparked a “rebranding” effort. Negative feelings about palliative decrease when it’s called “supportive care,” he said, and the new term is being adopted worldwide.

Dr. Hui reported having no financial disclosures.

SAN DIEGO – When it comes to aggressive care at the end of life, hematologists stand alone.

Hematology patients are more likely than are other patients to undergo chemotherapy and visit emergency departments and intensive care units when they’re near death, and they’re less likely to be referred for palliative care, according to David Hui, MD, an oncologist and palliative care specialist at the MD Anderson Cancer Center in Houston.

An analysis at the center, for example, found that 43% of hematology cancer patients received chemotherapy within the last 30 days of life, compared with 14% of patients with solid tumors.

“That’s not a number we’re proud of,” Dr. Hui said at the annual meeting of the American Society of Hematology. “Ultimately, at the end of life, do we want our patients to be in this setting? There is room for improvement.”

The cancer center isn’t an outlier on this front, Dr. Hui said. Data from other institutions in the United States and internationally confirm that hematologic oncologists tend to provide more aggressive care at the end of a patient’s life, compared with other cancer specialists.

“If you’re one of those patients, this is a very big deal,” said Dr. Hui, especially in light of data that suggest hematology patients get fewer referrals to palliative care than do other cancer patients. “Oncologists are optimistic, and hematologic oncologists especially,” he said.

Dr. Hui led a 2014 study of 816 adult cancer patients who died while under care at MD Anderson Cancer Center during 6 months in 2009 and 2010 (Cancer. 2014 May 15; 120[10]:1572-8).

“We found that patients with hematological malignancies were more likely to have multiple emergency room visits, intensive care unit admissions and death, and cancer treatments in the last weeks of life compared to patients with solid tumors,” the study authors wrote. “We also identified a relative lack of palliative care involvement in hematologic patients.”

Specifically, hematology cancer patients were much more likely to get aggressive end-of-life care than were the other cancer patients (odds ratio, 6.63, P less than .001).

Dr. Hui had led an earlier study that looked at the same 816 cancer patients and found that 45% had received palliative care consultations. But the researchers also found that patients with hematologic malignancies had significantly fewer palliative care referrals, the longest time between an advanced cancer diagnosis and a palliative care consultation, and one of the largest numbers of medical team encounters – a median of 38 – before palliative care (Oncologist. 2012;17[12]:1574-80).

In light of these numbers, policies at MD Anderson Cancer Center “are evolving rapidly,” Dr. Hui said.

He urged colleagues to think about the wishes of their patients. “What do patients really want? Good symptom control, time with family, not being a burden, not a prolonging dying process, having a sense of control during the middle of the turmoil.”

Dr. Hui added that the attitudes of oncologists regarding palliative care can affect whether patients get timely referrals to consultations. He led a 2016 study that surveyed 182 oncologists about end-of-life care and found that “many oncologists have a favorable attitude toward EOL care; this, in turn, was associated with greater provision of primary palliative care and higher rates of referral to specialist palliative care.”

However, “we found that hematologic oncology specialists expressed lower comfort levels compared with their solid tumor counterparts,” a finding that reflects the results of other studies, the study authors wrote (Oncologist. 2016 Sep;21[9]:1149-55).

The stigma surrounding palliative care is a sticking point, Dr. Hui said, and has sparked a “rebranding” effort. Negative feelings about palliative decrease when it’s called “supportive care,” he said, and the new term is being adopted worldwide.

Dr. Hui reported having no financial disclosures.