Multiple Myeloma

FLT3-ligand (FLT3-L) levels exceeding 92 pg/mL in bone marrow and 121 pg/mL in peripheral blood are associated with relapsed and refractory disease in patients with multiple myeloma, Normann Steiner, MD, and his colleagues report in a study published in PLoS ONE.

In the study of 14 patients with monoclonal gamm opathy of undetermined significance (MGUS), 42 patients with newly diagnosed myeloma, and 27 patients with relapsed/refractory myeloma, there was a 61% probability that patients with FLT3-L levels above 92 pg/mL in bone marrow had relapsed or refractory multiple myeloma and a 79% probability that those with FLT3-L levels of 92 pg/mL or less had not relapsed and were not refractory. Based on FLT3-L levels in peripheral blood, values of 121 pg/mL or more were associated with a 71% probability of relapsed or refractory disease. The likelihood of not having relapses or refractory disease was 87% for patients with values less than 121 pg/mL.

“FLT3-L could be useful as a marker to identify (relapsed or refractory multiple myeloma) patients and should be evaluated as a potential target for future therapy strategies,” Dr. Steiner of Innsbruck (Austria) Medical University, and his fellow researchers wrote in PLoS ONE.

The researchers obtained bone marrow aspirates from all patients. Peripheral blood was examined from 4 MGUS patients, 31 patients with newly diagnosed myeloma, and 16 patients with relapsed or refractory myeloma. Peripheral blood was also obtained from 16 control subjects.

The levels of four potential risk factors were measured – soluble TIE2, FLT3-L, endostatin, and osteoactivin. The most significant association with risk was seen with FLT3-L levels.

Expression of soluble TIE2 in bone marrow differed significantly among the three patient cohorts and may be driven by the same factors that influence FLT3-L levels. However, soluble TIE2 levels were not as effective at differentiating patients at risk for disease progression, the researchers wrote.

Soluble TIE2 expression in bone marrow was highest in MGUS patients (median 4003.97 pg/mL) in comparison to relapsed or refractory disease (median 2223.26 pg/mL; P = .03) and to newly diagnosed patients with myeloma (median 861.98 pg/mL; P less than .001). A statistically significant difference among bone marrow levels of soluble TIE2 was observed for newly diagnosed patients and those with relapsed or refractory disease (P = .03).

However, soluble TIE2 in peripheral blood plasma did not differ significantly in the three cohorts nor did it differ between patients and controls.

In contrast to TIE2 and FLT3-L, levels of endostatin were lowest (median 146.50 ng/mL) in bone marrow plasma samples of patients with relapsed or refractory disease. Levels were higher in MGUS patients (median 190.37 mg/dL) than in newly diagnosed myeloma patients (median 170.15 mg/mL; P = .5).

Similar to soluble TIE2, plasma levels of endostatin in peripheral blood did not differ significantly in the three patient cohorts. Measurements of endostatin in bone marrow and peripheral blood correlated significantly (P less than .001), and peripheral blood levels differed significantly (P less than .001) for patients and control persons.

Osteoactivin expression was highest in the MGUS cohort, with median bone marrow plasma levels of 36 ng/mL as compared with median levels of 24.92 ng/mL in newly diagnosed myeloma patients and 22.30 ng/mL in patients with relapsed or refractory myeloma. Osteoactivin levels in peripheral blood did not differ significantly in the three cohorts, but differed between patients and control subjects. Osteoactivin measures in bone marrow and peripheral blood correlated significantly.

Citation: Steiner N, et al. High levels of FLT3-ligand in bone marrow and peripheral blood of patients with advanced multiple myeloma. PLoS ONE 2017 Jul 20;12:e0181487. doi. org/10.1371/journal.pone.0181487.

[email protected]

On Twitter @maryjodales

FLT3-ligand (FLT3-L) levels exceeding 92 pg/mL in bone marrow and 121 pg/mL in peripheral blood are associated with relapsed and refractory disease in patients with multiple myeloma, Normann Steiner, MD, and his colleagues report in a study published in PLoS ONE.

In the study of 14 patients with monoclonal gamm opathy of undetermined significance (MGUS), 42 patients with newly diagnosed myeloma, and 27 patients with relapsed/refractory myeloma, there was a 61% probability that patients with FLT3-L levels above 92 pg/mL in bone marrow had relapsed or refractory multiple myeloma and a 79% probability that those with FLT3-L levels of 92 pg/mL or less had not relapsed and were not refractory. Based on FLT3-L levels in peripheral blood, values of 121 pg/mL or more were associated with a 71% probability of relapsed or refractory disease. The likelihood of not having relapses or refractory disease was 87% for patients with values less than 121 pg/mL.

“FLT3-L could be useful as a marker to identify (relapsed or refractory multiple myeloma) patients and should be evaluated as a potential target for future therapy strategies,” Dr. Steiner of Innsbruck (Austria) Medical University, and his fellow researchers wrote in PLoS ONE.

The researchers obtained bone marrow aspirates from all patients. Peripheral blood was examined from 4 MGUS patients, 31 patients with newly diagnosed myeloma, and 16 patients with relapsed or refractory myeloma. Peripheral blood was also obtained from 16 control subjects.

The levels of four potential risk factors were measured – soluble TIE2, FLT3-L, endostatin, and osteoactivin. The most significant association with risk was seen with FLT3-L levels.

Expression of soluble TIE2 in bone marrow differed significantly among the three patient cohorts and may be driven by the same factors that influence FLT3-L levels. However, soluble TIE2 levels were not as effective at differentiating patients at risk for disease progression, the researchers wrote.

Soluble TIE2 expression in bone marrow was highest in MGUS patients (median 4003.97 pg/mL) in comparison to relapsed or refractory disease (median 2223.26 pg/mL; P = .03) and to newly diagnosed patients with myeloma (median 861.98 pg/mL; P less than .001). A statistically significant difference among bone marrow levels of soluble TIE2 was observed for newly diagnosed patients and those with relapsed or refractory disease (P = .03).

However, soluble TIE2 in peripheral blood plasma did not differ significantly in the three cohorts nor did it differ between patients and controls.

In contrast to TIE2 and FLT3-L, levels of endostatin were lowest (median 146.50 ng/mL) in bone marrow plasma samples of patients with relapsed or refractory disease. Levels were higher in MGUS patients (median 190.37 mg/dL) than in newly diagnosed myeloma patients (median 170.15 mg/mL; P = .5).

Similar to soluble TIE2, plasma levels of endostatin in peripheral blood did not differ significantly in the three patient cohorts. Measurements of endostatin in bone marrow and peripheral blood correlated significantly (P less than .001), and peripheral blood levels differed significantly (P less than .001) for patients and control persons.

Osteoactivin expression was highest in the MGUS cohort, with median bone marrow plasma levels of 36 ng/mL as compared with median levels of 24.92 ng/mL in newly diagnosed myeloma patients and 22.30 ng/mL in patients with relapsed or refractory myeloma. Osteoactivin levels in peripheral blood did not differ significantly in the three cohorts, but differed between patients and control subjects. Osteoactivin measures in bone marrow and peripheral blood correlated significantly.

Citation: Steiner N, et al. High levels of FLT3-ligand in bone marrow and peripheral blood of patients with advanced multiple myeloma. PLoS ONE 2017 Jul 20;12:e0181487. doi. org/10.1371/journal.pone.0181487.

[email protected]

On Twitter @maryjodales

FLT3-ligand (FLT3-L) levels exceeding 92 pg/mL in bone marrow and 121 pg/mL in peripheral blood are associated with relapsed and refractory disease in patients with multiple myeloma, Normann Steiner, MD, and his colleagues report in a study published in PLoS ONE.

In the study of 14 patients with monoclonal gamm opathy of undetermined significance (MGUS), 42 patients with newly diagnosed myeloma, and 27 patients with relapsed/refractory myeloma, there was a 61% probability that patients with FLT3-L levels above 92 pg/mL in bone marrow had relapsed or refractory multiple myeloma and a 79% probability that those with FLT3-L levels of 92 pg/mL or less had not relapsed and were not refractory. Based on FLT3-L levels in peripheral blood, values of 121 pg/mL or more were associated with a 71% probability of relapsed or refractory disease. The likelihood of not having relapses or refractory disease was 87% for patients with values less than 121 pg/mL.

“FLT3-L could be useful as a marker to identify (relapsed or refractory multiple myeloma) patients and should be evaluated as a potential target for future therapy strategies,” Dr. Steiner of Innsbruck (Austria) Medical University, and his fellow researchers wrote in PLoS ONE.

The researchers obtained bone marrow aspirates from all patients. Peripheral blood was examined from 4 MGUS patients, 31 patients with newly diagnosed myeloma, and 16 patients with relapsed or refractory myeloma. Peripheral blood was also obtained from 16 control subjects.

The levels of four potential risk factors were measured – soluble TIE2, FLT3-L, endostatin, and osteoactivin. The most significant association with risk was seen with FLT3-L levels.

Expression of soluble TIE2 in bone marrow differed significantly among the three patient cohorts and may be driven by the same factors that influence FLT3-L levels. However, soluble TIE2 levels were not as effective at differentiating patients at risk for disease progression, the researchers wrote.

Soluble TIE2 expression in bone marrow was highest in MGUS patients (median 4003.97 pg/mL) in comparison to relapsed or refractory disease (median 2223.26 pg/mL; P = .03) and to newly diagnosed patients with myeloma (median 861.98 pg/mL; P less than .001). A statistically significant difference among bone marrow levels of soluble TIE2 was observed for newly diagnosed patients and those with relapsed or refractory disease (P = .03).

However, soluble TIE2 in peripheral blood plasma did not differ significantly in the three cohorts nor did it differ between patients and controls.

In contrast to TIE2 and FLT3-L, levels of endostatin were lowest (median 146.50 ng/mL) in bone marrow plasma samples of patients with relapsed or refractory disease. Levels were higher in MGUS patients (median 190.37 mg/dL) than in newly diagnosed myeloma patients (median 170.15 mg/mL; P = .5).

Similar to soluble TIE2, plasma levels of endostatin in peripheral blood did not differ significantly in the three patient cohorts. Measurements of endostatin in bone marrow and peripheral blood correlated significantly (P less than .001), and peripheral blood levels differed significantly (P less than .001) for patients and control persons.

Osteoactivin expression was highest in the MGUS cohort, with median bone marrow plasma levels of 36 ng/mL as compared with median levels of 24.92 ng/mL in newly diagnosed myeloma patients and 22.30 ng/mL in patients with relapsed or refractory myeloma. Osteoactivin levels in peripheral blood did not differ significantly in the three cohorts, but differed between patients and control subjects. Osteoactivin measures in bone marrow and peripheral blood correlated significantly.

Citation: Steiner N, et al. High levels of FLT3-ligand in bone marrow and peripheral blood of patients with advanced multiple myeloma. PLoS ONE 2017 Jul 20;12:e0181487. doi. org/10.1371/journal.pone.0181487.

[email protected]

On Twitter @maryjodales

MADRID – A four-drug induction regimen induced quicker and deeper remissions than sequential triplet regimens in patients with newly diagnosed multiple myeloma.

In addition, fast, deep remissions may lead to improved progression-free survival (PFS) following autologous stem cell transplantation (ASCT), said investigators from a U.K. Medical Research Council study.

In the phase 3 randomized, parallel group Myeloma XI study, very good partial responses (VGPR) or better were seen following induction in 79.5% of patients assigned to the quadruplet (KCRD) of carfilzomib (Kyprolis), cyclophosphamide, lenalidomide (Revlimid), and dexamethasone, compared with 60.8% for those assigned to cyclophosphamide, lenalidomide, and dexamethasone (CRD) and 52.8% for those assigned to cyclophosphamide, thalidomide, and dexamethasone (CTD), said Charlotte Pawlyn, MD, PhD, at the annual congress of the European Hematology Association.

“In our study, we see a very much deeper response after initial induction with the quadruplet regimen, compared with triplet regimens,” Dr. Pawlyn of the Institute of Cancer Research, London, said in an interview.

Medical Research Council investigators showed in the Myeloma IX study that among patients who had a less than VGPR to an immunomodulator-based triplet regimen such as CRD, a triplet regimen including the proteasome inhibitor bortezomib (Velcade) could improve both pre- and post-transplant response rates, and that the improved responses translated into improved PFS.

For the Myeloma XI study, the investigators employed the same response-adapted approach to compare outcomes following induction with the proteasome inhibitor–containing KCRD regimen and the lenalidomide- or thalidomide-based regimens.

Nancy B. Baron

[email protected]

MADRID – A four-drug induction regimen induced quicker and deeper remissions than sequential triplet regimens in patients with newly diagnosed multiple myeloma.

In addition, fast, deep remissions may lead to improved progression-free survival (PFS) following autologous stem cell transplantation (ASCT), said investigators from a U.K. Medical Research Council study.

In the phase 3 randomized, parallel group Myeloma XI study, very good partial responses (VGPR) or better were seen following induction in 79.5% of patients assigned to the quadruplet (KCRD) of carfilzomib (Kyprolis), cyclophosphamide, lenalidomide (Revlimid), and dexamethasone, compared with 60.8% for those assigned to cyclophosphamide, lenalidomide, and dexamethasone (CRD) and 52.8% for those assigned to cyclophosphamide, thalidomide, and dexamethasone (CTD), said Charlotte Pawlyn, MD, PhD, at the annual congress of the European Hematology Association.

“In our study, we see a very much deeper response after initial induction with the quadruplet regimen, compared with triplet regimens,” Dr. Pawlyn of the Institute of Cancer Research, London, said in an interview.

Medical Research Council investigators showed in the Myeloma IX study that among patients who had a less than VGPR to an immunomodulator-based triplet regimen such as CRD, a triplet regimen including the proteasome inhibitor bortezomib (Velcade) could improve both pre- and post-transplant response rates, and that the improved responses translated into improved PFS.

For the Myeloma XI study, the investigators employed the same response-adapted approach to compare outcomes following induction with the proteasome inhibitor–containing KCRD regimen and the lenalidomide- or thalidomide-based regimens.

Nancy B. Baron

[email protected]

MADRID – A four-drug induction regimen induced quicker and deeper remissions than sequential triplet regimens in patients with newly diagnosed multiple myeloma.

In addition, fast, deep remissions may lead to improved progression-free survival (PFS) following autologous stem cell transplantation (ASCT), said investigators from a U.K. Medical Research Council study.

In the phase 3 randomized, parallel group Myeloma XI study, very good partial responses (VGPR) or better were seen following induction in 79.5% of patients assigned to the quadruplet (KCRD) of carfilzomib (Kyprolis), cyclophosphamide, lenalidomide (Revlimid), and dexamethasone, compared with 60.8% for those assigned to cyclophosphamide, lenalidomide, and dexamethasone (CRD) and 52.8% for those assigned to cyclophosphamide, thalidomide, and dexamethasone (CTD), said Charlotte Pawlyn, MD, PhD, at the annual congress of the European Hematology Association.

“In our study, we see a very much deeper response after initial induction with the quadruplet regimen, compared with triplet regimens,” Dr. Pawlyn of the Institute of Cancer Research, London, said in an interview.

Medical Research Council investigators showed in the Myeloma IX study that among patients who had a less than VGPR to an immunomodulator-based triplet regimen such as CRD, a triplet regimen including the proteasome inhibitor bortezomib (Velcade) could improve both pre- and post-transplant response rates, and that the improved responses translated into improved PFS.

For the Myeloma XI study, the investigators employed the same response-adapted approach to compare outcomes following induction with the proteasome inhibitor–containing KCRD regimen and the lenalidomide- or thalidomide-based regimens.

Nancy B. Baron

[email protected]

Some studies have suggested that circulating plasma cells (CPCs) might have prognostic value in multiple myeloma (MM), but the findings remain controversial, say researchers from Zhengzhou University in the People’s Republic of China. However, the development of highly sensitive and specific diagnostic methods, such as polymerase chain reaction (PCR) and flow cytometry (FCM), the researchers say, make it possible to explore whether CPCs can serve as a biomarker in MM. To that end, they conducted the first meta-analysis to provide better insight into the prognostic value of CPCs in MM.

The researchers examined findings from 11 studies involving 2,943 patients in 5 countries. Peripheral blood samples were analyzed using FCM, PCR, slide-based immunofluorescence assay (IF), and conventional morphology (CM).

Circulating plasma cell status reflected aggressive disease more than tumor burden, the researchers say. Patients in the CPC-positive groups had more aggressive disease and a worse overall survival (OS) rate compared with patients in the CPC-negative groups. The presence of CPCs was “strikingly” associated with elevated the International Staging System score but not the Durie-Salm staging system (DS) score. This difference may be associated, the researchers suggest, with the fact that the DS stage predominantly reflects tumor burden, which is significantly reduced now by newer therapies.

In subgroup analyses, the patients in the FCM and CM  groups had worse prognosis for both disease progression and OS. The PCR subgroup showed prognostic significance for disease progression but not OS, and the IF subgroup for OS but not disease progression.

One question the researchers were also interested in answering was whether it mattered when the sample was taken. However, pooled hazard ratios for OS and disease progression were “fairly stable,” they say, and not influenced by sampling time. Regardless of whether CPCs are detected in an early stage or in relapse patients, the researchers add, CPC status may serve as a useful tool to guide treatment and prognosis.

Source:
Li J, Wang N, Tesfaluul N, Gao X, Liu S, Yue B. PLoS One. 2017;12(7):e0181447.
doi: 10.1371/journal.pone.0181447.

Some studies have suggested that circulating plasma cells (CPCs) might have prognostic value in multiple myeloma (MM), but the findings remain controversial, say researchers from Zhengzhou University in the People’s Republic of China. However, the development of highly sensitive and specific diagnostic methods, such as polymerase chain reaction (PCR) and flow cytometry (FCM), the researchers say, make it possible to explore whether CPCs can serve as a biomarker in MM. To that end, they conducted the first meta-analysis to provide better insight into the prognostic value of CPCs in MM.

The researchers examined findings from 11 studies involving 2,943 patients in 5 countries. Peripheral blood samples were analyzed using FCM, PCR, slide-based immunofluorescence assay (IF), and conventional morphology (CM).

Circulating plasma cell status reflected aggressive disease more than tumor burden, the researchers say. Patients in the CPC-positive groups had more aggressive disease and a worse overall survival (OS) rate compared with patients in the CPC-negative groups. The presence of CPCs was “strikingly” associated with elevated the International Staging System score but not the Durie-Salm staging system (DS) score. This difference may be associated, the researchers suggest, with the fact that the DS stage predominantly reflects tumor burden, which is significantly reduced now by newer therapies.

In subgroup analyses, the patients in the FCM and CM  groups had worse prognosis for both disease progression and OS. The PCR subgroup showed prognostic significance for disease progression but not OS, and the IF subgroup for OS but not disease progression.

One question the researchers were also interested in answering was whether it mattered when the sample was taken. However, pooled hazard ratios for OS and disease progression were “fairly stable,” they say, and not influenced by sampling time. Regardless of whether CPCs are detected in an early stage or in relapse patients, the researchers add, CPC status may serve as a useful tool to guide treatment and prognosis.

Source:
Li J, Wang N, Tesfaluul N, Gao X, Liu S, Yue B. PLoS One. 2017;12(7):e0181447.
doi: 10.1371/journal.pone.0181447.

Some studies have suggested that circulating plasma cells (CPCs) might have prognostic value in multiple myeloma (MM), but the findings remain controversial, say researchers from Zhengzhou University in the People’s Republic of China. However, the development of highly sensitive and specific diagnostic methods, such as polymerase chain reaction (PCR) and flow cytometry (FCM), the researchers say, make it possible to explore whether CPCs can serve as a biomarker in MM. To that end, they conducted the first meta-analysis to provide better insight into the prognostic value of CPCs in MM.

The researchers examined findings from 11 studies involving 2,943 patients in 5 countries. Peripheral blood samples were analyzed using FCM, PCR, slide-based immunofluorescence assay (IF), and conventional morphology (CM).

Circulating plasma cell status reflected aggressive disease more than tumor burden, the researchers say. Patients in the CPC-positive groups had more aggressive disease and a worse overall survival (OS) rate compared with patients in the CPC-negative groups. The presence of CPCs was “strikingly” associated with elevated the International Staging System score but not the Durie-Salm staging system (DS) score. This difference may be associated, the researchers suggest, with the fact that the DS stage predominantly reflects tumor burden, which is significantly reduced now by newer therapies.

In subgroup analyses, the patients in the FCM and CM  groups had worse prognosis for both disease progression and OS. The PCR subgroup showed prognostic significance for disease progression but not OS, and the IF subgroup for OS but not disease progression.

One question the researchers were also interested in answering was whether it mattered when the sample was taken. However, pooled hazard ratios for OS and disease progression were “fairly stable,” they say, and not influenced by sampling time. Regardless of whether CPCs are detected in an early stage or in relapse patients, the researchers add, CPC status may serve as a useful tool to guide treatment and prognosis.

Source:
Li J, Wang N, Tesfaluul N, Gao X, Liu S, Yue B. PLoS One. 2017;12(7):e0181447.
doi: 10.1371/journal.pone.0181447.

Micrograph showing MM

MADRID—New research suggests one triplet regimen may be more active but also more toxic than another in patients with newly diagnosed multiple myeloma (MM).

In the FORTE trial, the combination of carfilzomib, lenalidomide, and dexamethasone (KRD) produced higher response rates than carfilzomib, cyclophosphamide, and dexamethasone (KCD).

However, treatment with KRD also produced significantly more grade 3/4 non-hematologic adverse events (AEs) and serious AEs than the KCD regimen.

Francesca Gay, MD, PhD, of University of Torino in Italy, presented these results, from a planned interim analysis of FORTE, at the 22nd Congress of the European Hematology Association (EHA) as abstract S410.

The trial enrolled 477 MM patients younger than 65 years of age.

The patients were randomized to receive:

• Four 28-day KCD cycles (n=154)

  Carfilzomib at 20 mg/m² (for cycles 1 and 2) or 36 mg/m² (for subsequent cycles) on days 1, 2, 8, 9, 15, and 16

  Cyclophosphamide at 300 mg/m² on days 1, 8, and 15

  Dexamethasone at 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23

• Four 28-day KRD cycles (n=309)

  Carfilzomib and dexamethasone as above

  Lenalidomide at 25 mg on days 1-21

After the fourth induction cycle, all patients received cyclophosphamide at 2 g/m², followed by peripheral blood stem cell (PBSC) collection for autologous stem cell transplant.

Patient characteristics

The median age was 57 (range, 52-62) in the KCD arm and the KRD arm (range, 51-62). In both arms, 55% of patients were male.

Roughly half of patients in both arms had an ISS stage of I (52% in the KCD arm and 51% in the KRD arm), 31% of patients in both arms were stage II, and 17% were stage III.

Fifty-eight percent of patients in the KCD arm and 59% in the KRD arm did not have t(4;14), t(14;16), or del17. Thirty-one percent and 26%, respectively, did have one of these cytogenetic abnormalities. (For the remaining patients, cytogenetic risk data were missing.)

PBSC mobilization and response

The median number of PBSCs collected was 8.6 x 10⁶/kg in the KCD arm and 6.3 x 10⁶/kg in the KRD arm. Plerixafor was required in 6% of patients in the KCD arm and 28% of patients in the KRD arm (P<0.001).

Ninety-two percent of patients in the KCD arm and 96% in the KRD arm had a partial response or better. Sixty-one percent and 74%, respectively, had a very good partial response (P=0.01). Six percent and 15%, respectively, had a complete response.

Safety

Grade 3/4 hematologic AEs and serious AEs (in the KRD and KCD arms, respectively) were thrombocytopenia (2% and 1%), neutropenia (6% and 5%), and anemia (2% and 3%). Seven percent of KRD patients and 6% of KCD patients had at least 1 grade 3/4 or serious hematologic AE.

Grade 3/4 non-hematologic AEs and serious AEs (in the KRD and KCD arms, respectively) included dermatologic events (8% and 1%, P<0.001), renal events (1% and 2%), fever (4% and 1%), infections (5% and 3%), gastrointestinal AEs (2% and 1%), hepatic events (8% and 1%, P<0.001), venous thromboembolism (1% and 0%), hypertension (3% and 2%), and cardiac events (1% and 2%).

Thirty-two percent of KRD patients and 16% of KCD patients had at least 1 grade 3/4 or serious non-hematologic AE (P<0.001).

Four percent of patients in the KRD arm and 2% in the KCD arm discontinued treatment due to AEs. Fifteen percent and 6%, respectively, reduced the dose of at least 1 drug (P=0.005).

One percent of patients in the KRD arm and 2% in the KCD arm died from AEs. In the KCD arm, 1 patient had a sudden death, and 1 died of pneumonia. In the KRD arm, there was 1 sudden death in a patient with sepsis, 1 patient died of infection, and 1 died of cardiac arrest (this patient previously discontinued treatment due to renal failure).

Micrograph showing MM

MADRID—New research suggests one triplet regimen may be more active but also more toxic than another in patients with newly diagnosed multiple myeloma (MM).

In the FORTE trial, the combination of carfilzomib, lenalidomide, and dexamethasone (KRD) produced higher response rates than carfilzomib, cyclophosphamide, and dexamethasone (KCD).

However, treatment with KRD also produced significantly more grade 3/4 non-hematologic adverse events (AEs) and serious AEs than the KCD regimen.

Francesca Gay, MD, PhD, of University of Torino in Italy, presented these results, from a planned interim analysis of FORTE, at the 22nd Congress of the European Hematology Association (EHA) as abstract S410.

The trial enrolled 477 MM patients younger than 65 years of age.

The patients were randomized to receive:

• Four 28-day KCD cycles (n=154)

  Carfilzomib at 20 mg/m² (for cycles 1 and 2) or 36 mg/m² (for subsequent cycles) on days 1, 2, 8, 9, 15, and 16

  Cyclophosphamide at 300 mg/m² on days 1, 8, and 15

  Dexamethasone at 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23

• Four 28-day KRD cycles (n=309)

  Carfilzomib and dexamethasone as above

  Lenalidomide at 25 mg on days 1-21

After the fourth induction cycle, all patients received cyclophosphamide at 2 g/m², followed by peripheral blood stem cell (PBSC) collection for autologous stem cell transplant.

Patient characteristics

The median age was 57 (range, 52-62) in the KCD arm and the KRD arm (range, 51-62). In both arms, 55% of patients were male.

Roughly half of patients in both arms had an ISS stage of I (52% in the KCD arm and 51% in the KRD arm), 31% of patients in both arms were stage II, and 17% were stage III.

Fifty-eight percent of patients in the KCD arm and 59% in the KRD arm did not have t(4;14), t(14;16), or del17. Thirty-one percent and 26%, respectively, did have one of these cytogenetic abnormalities. (For the remaining patients, cytogenetic risk data were missing.)

PBSC mobilization and response

The median number of PBSCs collected was 8.6 x 10⁶/kg in the KCD arm and 6.3 x 10⁶/kg in the KRD arm. Plerixafor was required in 6% of patients in the KCD arm and 28% of patients in the KRD arm (P<0.001).

Ninety-two percent of patients in the KCD arm and 96% in the KRD arm had a partial response or better. Sixty-one percent and 74%, respectively, had a very good partial response (P=0.01). Six percent and 15%, respectively, had a complete response.

Safety

Grade 3/4 hematologic AEs and serious AEs (in the KRD and KCD arms, respectively) were thrombocytopenia (2% and 1%), neutropenia (6% and 5%), and anemia (2% and 3%). Seven percent of KRD patients and 6% of KCD patients had at least 1 grade 3/4 or serious hematologic AE.

Grade 3/4 non-hematologic AEs and serious AEs (in the KRD and KCD arms, respectively) included dermatologic events (8% and 1%, P<0.001), renal events (1% and 2%), fever (4% and 1%), infections (5% and 3%), gastrointestinal AEs (2% and 1%), hepatic events (8% and 1%, P<0.001), venous thromboembolism (1% and 0%), hypertension (3% and 2%), and cardiac events (1% and 2%).

Thirty-two percent of KRD patients and 16% of KCD patients had at least 1 grade 3/4 or serious non-hematologic AE (P<0.001).

Four percent of patients in the KRD arm and 2% in the KCD arm discontinued treatment due to AEs. Fifteen percent and 6%, respectively, reduced the dose of at least 1 drug (P=0.005).

One percent of patients in the KRD arm and 2% in the KCD arm died from AEs. In the KCD arm, 1 patient had a sudden death, and 1 died of pneumonia. In the KRD arm, there was 1 sudden death in a patient with sepsis, 1 patient died of infection, and 1 died of cardiac arrest (this patient previously discontinued treatment due to renal failure).

Micrograph showing MM

MADRID—New research suggests one triplet regimen may be more active but also more toxic than another in patients with newly diagnosed multiple myeloma (MM).

In the FORTE trial, the combination of carfilzomib, lenalidomide, and dexamethasone (KRD) produced higher response rates than carfilzomib, cyclophosphamide, and dexamethasone (KCD).

However, treatment with KRD also produced significantly more grade 3/4 non-hematologic adverse events (AEs) and serious AEs than the KCD regimen.

Francesca Gay, MD, PhD, of University of Torino in Italy, presented these results, from a planned interim analysis of FORTE, at the 22nd Congress of the European Hematology Association (EHA) as abstract S410.

The trial enrolled 477 MM patients younger than 65 years of age.

The patients were randomized to receive:

• Four 28-day KCD cycles (n=154)

  Carfilzomib at 20 mg/m² (for cycles 1 and 2) or 36 mg/m² (for subsequent cycles) on days 1, 2, 8, 9, 15, and 16

  Cyclophosphamide at 300 mg/m² on days 1, 8, and 15

  Dexamethasone at 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23

• Four 28-day KRD cycles (n=309)

  Carfilzomib and dexamethasone as above

  Lenalidomide at 25 mg on days 1-21

After the fourth induction cycle, all patients received cyclophosphamide at 2 g/m², followed by peripheral blood stem cell (PBSC) collection for autologous stem cell transplant.

Patient characteristics

The median age was 57 (range, 52-62) in the KCD arm and the KRD arm (range, 51-62). In both arms, 55% of patients were male.

Roughly half of patients in both arms had an ISS stage of I (52% in the KCD arm and 51% in the KRD arm), 31% of patients in both arms were stage II, and 17% were stage III.

Fifty-eight percent of patients in the KCD arm and 59% in the KRD arm did not have t(4;14), t(14;16), or del17. Thirty-one percent and 26%, respectively, did have one of these cytogenetic abnormalities. (For the remaining patients, cytogenetic risk data were missing.)

PBSC mobilization and response

The median number of PBSCs collected was 8.6 x 10⁶/kg in the KCD arm and 6.3 x 10⁶/kg in the KRD arm. Plerixafor was required in 6% of patients in the KCD arm and 28% of patients in the KRD arm (P<0.001).

Ninety-two percent of patients in the KCD arm and 96% in the KRD arm had a partial response or better. Sixty-one percent and 74%, respectively, had a very good partial response (P=0.01). Six percent and 15%, respectively, had a complete response.

Safety

Grade 3/4 hematologic AEs and serious AEs (in the KRD and KCD arms, respectively) were thrombocytopenia (2% and 1%), neutropenia (6% and 5%), and anemia (2% and 3%). Seven percent of KRD patients and 6% of KCD patients had at least 1 grade 3/4 or serious hematologic AE.

Grade 3/4 non-hematologic AEs and serious AEs (in the KRD and KCD arms, respectively) included dermatologic events (8% and 1%, P<0.001), renal events (1% and 2%), fever (4% and 1%), infections (5% and 3%), gastrointestinal AEs (2% and 1%), hepatic events (8% and 1%, P<0.001), venous thromboembolism (1% and 0%), hypertension (3% and 2%), and cardiac events (1% and 2%).

Thirty-two percent of KRD patients and 16% of KCD patients had at least 1 grade 3/4 or serious non-hematologic AE (P<0.001).

Four percent of patients in the KRD arm and 2% in the KCD arm discontinued treatment due to AEs. Fifteen percent and 6%, respectively, reduced the dose of at least 1 drug (P=0.005).

One percent of patients in the KRD arm and 2% in the KCD arm died from AEs. In the KCD arm, 1 patient had a sudden death, and 1 died of pneumonia. In the KRD arm, there was 1 sudden death in a patient with sepsis, 1 patient died of infection, and 1 died of cardiac arrest (this patient previously discontinued treatment due to renal failure).

Photo by Rhoda Baer

New research suggests young cancer survivors struggle to get their social lives “back to normal” within the first 2 years of their diagnosis.

The study showed that adolescents and young adults (AYAs) with cancer had significantly worse social functioning than the general population around the time of cancer diagnosis as well as 1 year and 2 years later.

These findings were published in Cancer.

“The research is important to help these young survivors better reintegrate into society,” said study author Brad Zebrack, PhD, of the University of Michigan in Ann Arbor.

He and his colleagues collected data from 141 AYA cancer patients (ages 14 to 39) who visited 1 of 5 US medical facilities between March 2008 and April 2010.

The patients completed a self-report measure of social functioning within the first 4 months of diagnosis, then again at 12 months and 24 months.

Compared to the general population, the AYA cancer patients had significantly worse social functioning scores at all time points:

• Around the time of diagnosis—52.0 vs 85.1 (P<0.001)
• At 12 months—73.1 vs 85.1 (P<0.001)
• At 24 months—69.2 vs 85.1 (P<0.001).

Overall, the patients did experience improvements in social functioning from baseline to the 12-month time point, but their scores remained stable after that.

The researchers noted that 9% of patients had consistently high/normal social functioning, 47% had improvements in social functioning over time, 13% had worsening social functioning over time, and 32% had consistently low social functioning.

“This finding highlights the need to screen, identify, and respond to the needs of high-risk young adult-adolescent patients at the time of diagnosis and then monitor them over time,” Dr Zebrack said.

“They are likely the ones most in need of help in managing work, school, and potentially problematic relationships with family members and friends.”

Photo by Rhoda Baer

New research suggests young cancer survivors struggle to get their social lives “back to normal” within the first 2 years of their diagnosis.

The study showed that adolescents and young adults (AYAs) with cancer had significantly worse social functioning than the general population around the time of cancer diagnosis as well as 1 year and 2 years later.

These findings were published in Cancer.

“The research is important to help these young survivors better reintegrate into society,” said study author Brad Zebrack, PhD, of the University of Michigan in Ann Arbor.

He and his colleagues collected data from 141 AYA cancer patients (ages 14 to 39) who visited 1 of 5 US medical facilities between March 2008 and April 2010.

The patients completed a self-report measure of social functioning within the first 4 months of diagnosis, then again at 12 months and 24 months.

Compared to the general population, the AYA cancer patients had significantly worse social functioning scores at all time points:

• Around the time of diagnosis—52.0 vs 85.1 (P<0.001)
• At 12 months—73.1 vs 85.1 (P<0.001)
• At 24 months—69.2 vs 85.1 (P<0.001).

Overall, the patients did experience improvements in social functioning from baseline to the 12-month time point, but their scores remained stable after that.

The researchers noted that 9% of patients had consistently high/normal social functioning, 47% had improvements in social functioning over time, 13% had worsening social functioning over time, and 32% had consistently low social functioning.

“This finding highlights the need to screen, identify, and respond to the needs of high-risk young adult-adolescent patients at the time of diagnosis and then monitor them over time,” Dr Zebrack said.

“They are likely the ones most in need of help in managing work, school, and potentially problematic relationships with family members and friends.”

Photo by Rhoda Baer

New research suggests young cancer survivors struggle to get their social lives “back to normal” within the first 2 years of their diagnosis.

The study showed that adolescents and young adults (AYAs) with cancer had significantly worse social functioning than the general population around the time of cancer diagnosis as well as 1 year and 2 years later.

These findings were published in Cancer.

“The research is important to help these young survivors better reintegrate into society,” said study author Brad Zebrack, PhD, of the University of Michigan in Ann Arbor.

He and his colleagues collected data from 141 AYA cancer patients (ages 14 to 39) who visited 1 of 5 US medical facilities between March 2008 and April 2010.

The patients completed a self-report measure of social functioning within the first 4 months of diagnosis, then again at 12 months and 24 months.

Compared to the general population, the AYA cancer patients had significantly worse social functioning scores at all time points:

• Around the time of diagnosis—52.0 vs 85.1 (P<0.001)
• At 12 months—73.1 vs 85.1 (P<0.001)
• At 24 months—69.2 vs 85.1 (P<0.001).

Overall, the patients did experience improvements in social functioning from baseline to the 12-month time point, but their scores remained stable after that.

The researchers noted that 9% of patients had consistently high/normal social functioning, 47% had improvements in social functioning over time, 13% had worsening social functioning over time, and 32% had consistently low social functioning.

“This finding highlights the need to screen, identify, and respond to the needs of high-risk young adult-adolescent patients at the time of diagnosis and then monitor them over time,” Dr Zebrack said.

“They are likely the ones most in need of help in managing work, school, and potentially problematic relationships with family members and friends.”

Carfilzomib, a selective second-generation proteasome inhibitor, has performed well in clinical trials. So because other “triplets”—combinations of alkylator, proteasome inhibitor, and steroid—had shown “encouraging” response rates, researchers from the Center for Cancer and Blood Disorders in Bethesda, Maryland, and others, conducted a multicenter study to evaluate the safety and tolerability of twice-weekly carfilzomib combined with cyclophosphamide and dexamethasone (KCyd) for patients newly diagnosed with multiple myeloma (MM).

The researchers tested 3 doses of carfilzomib: 36 mg/m², 45 mg/m², and 56 mg/m². Of the 22 enrolled patients, 16 were treated with the maximum dose.

Fourteen patients completed all 8 cycles of treatment; 10 in the maximum-dose group completed all 8. At 56 mg/m², the overall response rate was 87.5%. Among the 14 patients whose disease responded to therapy, the median time to response was 1 month.

Five patients discontinued treatment because of adverse effects (AEs), but the researchers found no dose-limiting toxicities at any of the dose levels. The most common AEs were nausea, diarrhea, and anemia.

The researchers concluded that based on previous research, KCyd with 36 mg/m² is safe and effective in patients aged ≥ 65 years with newly diagnosed MM. However, their findings suggest that twice-weekly carfilzomib 56 mg/m² in combination with cyclophosphamide and dexamethasone also is effective with “manageable toxicity.”

Source:
Boccia RV, Bessudo A, Agajanian R, et al. Clin Lymphoma Myeloma Leuk. In press.
doi: 10.1016/j.clml.2017.05.009.

Carfilzomib, a selective second-generation proteasome inhibitor, has performed well in clinical trials. So because other “triplets”—combinations of alkylator, proteasome inhibitor, and steroid—had shown “encouraging” response rates, researchers from the Center for Cancer and Blood Disorders in Bethesda, Maryland, and others, conducted a multicenter study to evaluate the safety and tolerability of twice-weekly carfilzomib combined with cyclophosphamide and dexamethasone (KCyd) for patients newly diagnosed with multiple myeloma (MM).

The researchers tested 3 doses of carfilzomib: 36 mg/m², 45 mg/m², and 56 mg/m². Of the 22 enrolled patients, 16 were treated with the maximum dose.

Fourteen patients completed all 8 cycles of treatment; 10 in the maximum-dose group completed all 8. At 56 mg/m², the overall response rate was 87.5%. Among the 14 patients whose disease responded to therapy, the median time to response was 1 month.

Five patients discontinued treatment because of adverse effects (AEs), but the researchers found no dose-limiting toxicities at any of the dose levels. The most common AEs were nausea, diarrhea, and anemia.

The researchers concluded that based on previous research, KCyd with 36 mg/m² is safe and effective in patients aged ≥ 65 years with newly diagnosed MM. However, their findings suggest that twice-weekly carfilzomib 56 mg/m² in combination with cyclophosphamide and dexamethasone also is effective with “manageable toxicity.”

Source:
Boccia RV, Bessudo A, Agajanian R, et al. Clin Lymphoma Myeloma Leuk. In press.
doi: 10.1016/j.clml.2017.05.009.

Carfilzomib, a selective second-generation proteasome inhibitor, has performed well in clinical trials. So because other “triplets”—combinations of alkylator, proteasome inhibitor, and steroid—had shown “encouraging” response rates, researchers from the Center for Cancer and Blood Disorders in Bethesda, Maryland, and others, conducted a multicenter study to evaluate the safety and tolerability of twice-weekly carfilzomib combined with cyclophosphamide and dexamethasone (KCyd) for patients newly diagnosed with multiple myeloma (MM).

The researchers tested 3 doses of carfilzomib: 36 mg/m², 45 mg/m², and 56 mg/m². Of the 22 enrolled patients, 16 were treated with the maximum dose.

Fourteen patients completed all 8 cycles of treatment; 10 in the maximum-dose group completed all 8. At 56 mg/m², the overall response rate was 87.5%. Among the 14 patients whose disease responded to therapy, the median time to response was 1 month.

Five patients discontinued treatment because of adverse effects (AEs), but the researchers found no dose-limiting toxicities at any of the dose levels. The most common AEs were nausea, diarrhea, and anemia.

The researchers concluded that based on previous research, KCyd with 36 mg/m² is safe and effective in patients aged ≥ 65 years with newly diagnosed MM. However, their findings suggest that twice-weekly carfilzomib 56 mg/m² in combination with cyclophosphamide and dexamethasone also is effective with “manageable toxicity.”

Source:
Boccia RV, Bessudo A, Agajanian R, et al. Clin Lymphoma Myeloma Leuk. In press.
doi: 10.1016/j.clml.2017.05.009.

Beckman Coulter has been authorized to market its ClearLLab Reagents (T1, T2, B1, B2, M) tests for use with flow cytometry to detect leukemias, lymphomas, and myeloproliferative disorders in blood, bone marrow, and lymph nodes, according to the U.S. Food and Drug Administration.

[email protected]

Beckman Coulter has been authorized to market its ClearLLab Reagents (T1, T2, B1, B2, M) tests for use with flow cytometry to detect leukemias, lymphomas, and myeloproliferative disorders in blood, bone marrow, and lymph nodes, according to the U.S. Food and Drug Administration.

[email protected]

Beckman Coulter has been authorized to market its ClearLLab Reagents (T1, T2, B1, B2, M) tests for use with flow cytometry to detect leukemias, lymphomas, and myeloproliferative disorders in blood, bone marrow, and lymph nodes, according to the U.S. Food and Drug Administration.

[email protected]

MADRID – The risk of osteoporotic fracture associated with hematopoietic stem cell transplantation (HSCT) could be assessed using the Fracture Risk Assessment Tool (FRAX), researchers from the University of Texas MD Anderson Cancer Center have found.

In a retrospective cohort study, Huifang Lu, MD, and her collaborators found that FRAX could predict the risk of fracture with reasonable accuracy. The area under the receiver operating characteristic curve was 0.66 for predicting a fracture 10 years after HSCT.

“Current guidelines recommend the evaluation of bone health at 1 year following the transplant, but we recommend that this needs to happen at a much earlier time,” Dr. Lu said at the European Congress of Rheumatology.

Determining how to assess risk earlier and prevent bone loss remains a challenge, however. FRAX is an easy and quick tool to use, but its predictive ability is modest, she said.

As the finding comes from a retrospective study, prospective evaluation of FRAX is needed in HSCT patients. If shown predictive in this setting, bone health could be assessed earlier using FRAX, ideally at or before the time of the transplant, to allow appropriate action to be taken, such as prescribing bisphosphonates to those identified to be at high risk.

There is no consensus on preventing and treating bone loss following HSCT, said Dr. Lu. In a meta-analysis performed by Dr. Lu and her associates (Bone Marrow Transplant. 2017;52[5]:663-70), less bone loss was seen in patients who received a bisphosphonate.

As the use of HSCT has expanded over the past two decades, there is an expanding population of survivors with potential long-term effects such as bone loss and a higher risk of fractures, compared with the general population, Dr. Lu explained.

The FRAX tool takes into account pre-HSCT factors such as age, smoking status, alcohol use, prior fracture, body mass index, and corticosteroid use. This can be considered in association with the fracture risk related to the various conditioning and supporting regimens that patients receive around the time of their transplants.

The study included 5,170 adult patients who had undergone HSCT at the University of Texas MD Anderson Cancer Center over a 10-year period. Patients were considered to have entered the cohort at the time of their transplants, Dr. Lu said. Their history of osteoporotic fractures up to 3.3 years later was obtained and verified by radiology and physician assessment. FRAX probabilities were then derived from baseline information.

The mean age of patients included was 52 years, 57% were male and 75% were white. One-quarter had experienced a prior fracture. Of note, 26% of the cohort underwent HSCT for multiple myeloma, 70% of whom had already had a fracture, compared with 9% of those who underwent HSCT for another reason such as leukemia or lymphoma.

Multivariate analyses were performed with and without considering death as a competing risk, and similar results were obtained. Higher FRAX scores (20 or greater) were more likely to be recorded in individuals who sustained a fracture than in those who did not. Patients who had an allogeneic HSCT were 15% more likely to have a fracture as those who received an autologous transplant. Perhaps not surprisingly, patients with multiple myeloma were more likely than those who had HSCT for other reasons to sustain a fracture by 10 years based on FRAX results (hazard ratio, 3.16).

Future research needs to look at the optimal cut offs for FRAX scores predictive of events and see if there is any association between the loss of bone and fracture risk. There also needs to be an evaluation of the use of concomitant medications and health economic analyses performed.

Dr. Lu had no conflicts of interest. The study was funded by the Rolanette and Berdon Lawrence Bone Disease Program of Texas and via Cancer Survivorship Research Seed Monday Grants from the University Cancer Foundation and Duncan Family Institute for Cancer Prevention and Risk Assessment to the University of Texas MD Anderson Cancer Center.

MADRID – The risk of osteoporotic fracture associated with hematopoietic stem cell transplantation (HSCT) could be assessed using the Fracture Risk Assessment Tool (FRAX), researchers from the University of Texas MD Anderson Cancer Center have found.

In a retrospective cohort study, Huifang Lu, MD, and her collaborators found that FRAX could predict the risk of fracture with reasonable accuracy. The area under the receiver operating characteristic curve was 0.66 for predicting a fracture 10 years after HSCT.

“Current guidelines recommend the evaluation of bone health at 1 year following the transplant, but we recommend that this needs to happen at a much earlier time,” Dr. Lu said at the European Congress of Rheumatology.

Determining how to assess risk earlier and prevent bone loss remains a challenge, however. FRAX is an easy and quick tool to use, but its predictive ability is modest, she said.

As the finding comes from a retrospective study, prospective evaluation of FRAX is needed in HSCT patients. If shown predictive in this setting, bone health could be assessed earlier using FRAX, ideally at or before the time of the transplant, to allow appropriate action to be taken, such as prescribing bisphosphonates to those identified to be at high risk.

There is no consensus on preventing and treating bone loss following HSCT, said Dr. Lu. In a meta-analysis performed by Dr. Lu and her associates (Bone Marrow Transplant. 2017;52[5]:663-70), less bone loss was seen in patients who received a bisphosphonate.

As the use of HSCT has expanded over the past two decades, there is an expanding population of survivors with potential long-term effects such as bone loss and a higher risk of fractures, compared with the general population, Dr. Lu explained.

The FRAX tool takes into account pre-HSCT factors such as age, smoking status, alcohol use, prior fracture, body mass index, and corticosteroid use. This can be considered in association with the fracture risk related to the various conditioning and supporting regimens that patients receive around the time of their transplants.

The study included 5,170 adult patients who had undergone HSCT at the University of Texas MD Anderson Cancer Center over a 10-year period. Patients were considered to have entered the cohort at the time of their transplants, Dr. Lu said. Their history of osteoporotic fractures up to 3.3 years later was obtained and verified by radiology and physician assessment. FRAX probabilities were then derived from baseline information.

The mean age of patients included was 52 years, 57% were male and 75% were white. One-quarter had experienced a prior fracture. Of note, 26% of the cohort underwent HSCT for multiple myeloma, 70% of whom had already had a fracture, compared with 9% of those who underwent HSCT for another reason such as leukemia or lymphoma.

Multivariate analyses were performed with and without considering death as a competing risk, and similar results were obtained. Higher FRAX scores (20 or greater) were more likely to be recorded in individuals who sustained a fracture than in those who did not. Patients who had an allogeneic HSCT were 15% more likely to have a fracture as those who received an autologous transplant. Perhaps not surprisingly, patients with multiple myeloma were more likely than those who had HSCT for other reasons to sustain a fracture by 10 years based on FRAX results (hazard ratio, 3.16).

Future research needs to look at the optimal cut offs for FRAX scores predictive of events and see if there is any association between the loss of bone and fracture risk. There also needs to be an evaluation of the use of concomitant medications and health economic analyses performed.

Dr. Lu had no conflicts of interest. The study was funded by the Rolanette and Berdon Lawrence Bone Disease Program of Texas and via Cancer Survivorship Research Seed Monday Grants from the University Cancer Foundation and Duncan Family Institute for Cancer Prevention and Risk Assessment to the University of Texas MD Anderson Cancer Center.

MADRID – The risk of osteoporotic fracture associated with hematopoietic stem cell transplantation (HSCT) could be assessed using the Fracture Risk Assessment Tool (FRAX), researchers from the University of Texas MD Anderson Cancer Center have found.

In a retrospective cohort study, Huifang Lu, MD, and her collaborators found that FRAX could predict the risk of fracture with reasonable accuracy. The area under the receiver operating characteristic curve was 0.66 for predicting a fracture 10 years after HSCT.

“Current guidelines recommend the evaluation of bone health at 1 year following the transplant, but we recommend that this needs to happen at a much earlier time,” Dr. Lu said at the European Congress of Rheumatology.

Determining how to assess risk earlier and prevent bone loss remains a challenge, however. FRAX is an easy and quick tool to use, but its predictive ability is modest, she said.

As the finding comes from a retrospective study, prospective evaluation of FRAX is needed in HSCT patients. If shown predictive in this setting, bone health could be assessed earlier using FRAX, ideally at or before the time of the transplant, to allow appropriate action to be taken, such as prescribing bisphosphonates to those identified to be at high risk.

There is no consensus on preventing and treating bone loss following HSCT, said Dr. Lu. In a meta-analysis performed by Dr. Lu and her associates (Bone Marrow Transplant. 2017;52[5]:663-70), less bone loss was seen in patients who received a bisphosphonate.

As the use of HSCT has expanded over the past two decades, there is an expanding population of survivors with potential long-term effects such as bone loss and a higher risk of fractures, compared with the general population, Dr. Lu explained.

The FRAX tool takes into account pre-HSCT factors such as age, smoking status, alcohol use, prior fracture, body mass index, and corticosteroid use. This can be considered in association with the fracture risk related to the various conditioning and supporting regimens that patients receive around the time of their transplants.

The study included 5,170 adult patients who had undergone HSCT at the University of Texas MD Anderson Cancer Center over a 10-year period. Patients were considered to have entered the cohort at the time of their transplants, Dr. Lu said. Their history of osteoporotic fractures up to 3.3 years later was obtained and verified by radiology and physician assessment. FRAX probabilities were then derived from baseline information.

The mean age of patients included was 52 years, 57% were male and 75% were white. One-quarter had experienced a prior fracture. Of note, 26% of the cohort underwent HSCT for multiple myeloma, 70% of whom had already had a fracture, compared with 9% of those who underwent HSCT for another reason such as leukemia or lymphoma.

Multivariate analyses were performed with and without considering death as a competing risk, and similar results were obtained. Higher FRAX scores (20 or greater) were more likely to be recorded in individuals who sustained a fracture than in those who did not. Patients who had an allogeneic HSCT were 15% more likely to have a fracture as those who received an autologous transplant. Perhaps not surprisingly, patients with multiple myeloma were more likely than those who had HSCT for other reasons to sustain a fracture by 10 years based on FRAX results (hazard ratio, 3.16).

Future research needs to look at the optimal cut offs for FRAX scores predictive of events and see if there is any association between the loss of bone and fracture risk. There also needs to be an evaluation of the use of concomitant medications and health economic analyses performed.

Dr. Lu had no conflicts of interest. The study was funded by the Rolanette and Berdon Lawrence Bone Disease Program of Texas and via Cancer Survivorship Research Seed Monday Grants from the University Cancer Foundation and Duncan Family Institute for Cancer Prevention and Risk Assessment to the University of Texas MD Anderson Cancer Center.

Lab mouse

Preclinical research suggests a targeted therapy may be able to rebuild and strengthen bone in patients with multiple myeloma (MM).

Researchers tested an antibody targeting the protein sclerostin, an important regulator of bone formation, in mouse models of MM.

The antibody prevented bone loss and even increased bone volume in the mice.

The treatment also made bones more resistant to fracture and worked synergistically with zoledronic acid.

Michelle McDonald, PhD, of the Garvan Institute of Medical Research in Sydney, New South Wales, Australia, and her colleagues reported these findings in Blood.

“Multiple myeloma is a cancer that grows in bone, and, in most patients, it is associated with widespread bone loss and recurrent bone fractures, which can be extremely painful and debilitating,” Dr McDonald said.

“The current treatment for myeloma-associated bone disease with bisphosphonate drugs prevents further bone loss, but it doesn’t fix damaged bones, so patients continue to fracture. We wanted to re-stimulate bone formation and increase bone strength and resistance to fracture.”

So the researchers tested an antibody that targets and neutralizes sclerostin. In clinical studies of osteoporosis, such antibodies have been shown to increase bone mass and reduce fracture incidence.

In the mouse models of MM, the antibody prevented further bone loss and even doubled bone volume in some of the mice.

“When we looked at the bones before and after treatment, the difference was remarkable,” Dr McDonald said. “We saw less lesions or ‘holes’ in the bones after anti-sclerostin treatment. These lesions are the primary cause of bone pain, so this is an extremely important result.”

The treatment also made the bones substantially stronger, with more than double the resistance to fracture observed in many of the tests.

The researchers then combined the antibody with the bisphosphonate zoledronic acid and observed positive results.

“Bisphosphonates work by preventing bone breakdown, so we combined zoledronic acid with the new anti-sclerostin antibody that rebuilds bone,” Dr McDonald said. “Together, the impact on bone thickness, strength, and resistance to fracture was greater than either treatment alone.”

The researchers said these findings suggest a potential new strategy for reducing fractures in patients with MM.

“[M]yelomas, like other cancers, vary from individual to individual and can therefore be difficult to target,” said study author Peter I. Croucher, PhD, of the Garvan Institute of Medical Research.

“By targeting sclerostin, we are blocking a protein that is active in every person’s bones and not something unique to a person’s cancer. Therefore, in the future, when we test this antibody in humans, we are hopeful to see a response in most, if not all, patients.”

“We are now looking towards clinical trials for this antibody and, in the future, development of this type of therapy for the clinical treatment of multiple myeloma. This therapeutic approach has the potential to transform the prognosis for myeloma patients, enhancing quality of life, and ultimately reducing mortality. It also has clinical implications for the treatment of other cancers that develop in the skeleton.” 

Lab mouse

Preclinical research suggests a targeted therapy may be able to rebuild and strengthen bone in patients with multiple myeloma (MM).

Researchers tested an antibody targeting the protein sclerostin, an important regulator of bone formation, in mouse models of MM.

The antibody prevented bone loss and even increased bone volume in the mice.

The treatment also made bones more resistant to fracture and worked synergistically with zoledronic acid.

Michelle McDonald, PhD, of the Garvan Institute of Medical Research in Sydney, New South Wales, Australia, and her colleagues reported these findings in Blood.

“Multiple myeloma is a cancer that grows in bone, and, in most patients, it is associated with widespread bone loss and recurrent bone fractures, which can be extremely painful and debilitating,” Dr McDonald said.

“The current treatment for myeloma-associated bone disease with bisphosphonate drugs prevents further bone loss, but it doesn’t fix damaged bones, so patients continue to fracture. We wanted to re-stimulate bone formation and increase bone strength and resistance to fracture.”

So the researchers tested an antibody that targets and neutralizes sclerostin. In clinical studies of osteoporosis, such antibodies have been shown to increase bone mass and reduce fracture incidence.

In the mouse models of MM, the antibody prevented further bone loss and even doubled bone volume in some of the mice.

“When we looked at the bones before and after treatment, the difference was remarkable,” Dr McDonald said. “We saw less lesions or ‘holes’ in the bones after anti-sclerostin treatment. These lesions are the primary cause of bone pain, so this is an extremely important result.”

The treatment also made the bones substantially stronger, with more than double the resistance to fracture observed in many of the tests.

The researchers then combined the antibody with the bisphosphonate zoledronic acid and observed positive results.

“Bisphosphonates work by preventing bone breakdown, so we combined zoledronic acid with the new anti-sclerostin antibody that rebuilds bone,” Dr McDonald said. “Together, the impact on bone thickness, strength, and resistance to fracture was greater than either treatment alone.”

The researchers said these findings suggest a potential new strategy for reducing fractures in patients with MM.

“[M]yelomas, like other cancers, vary from individual to individual and can therefore be difficult to target,” said study author Peter I. Croucher, PhD, of the Garvan Institute of Medical Research.

“By targeting sclerostin, we are blocking a protein that is active in every person’s bones and not something unique to a person’s cancer. Therefore, in the future, when we test this antibody in humans, we are hopeful to see a response in most, if not all, patients.”

“We are now looking towards clinical trials for this antibody and, in the future, development of this type of therapy for the clinical treatment of multiple myeloma. This therapeutic approach has the potential to transform the prognosis for myeloma patients, enhancing quality of life, and ultimately reducing mortality. It also has clinical implications for the treatment of other cancers that develop in the skeleton.” 

Lab mouse

Preclinical research suggests a targeted therapy may be able to rebuild and strengthen bone in patients with multiple myeloma (MM).

Researchers tested an antibody targeting the protein sclerostin, an important regulator of bone formation, in mouse models of MM.

The antibody prevented bone loss and even increased bone volume in the mice.

The treatment also made bones more resistant to fracture and worked synergistically with zoledronic acid.

Michelle McDonald, PhD, of the Garvan Institute of Medical Research in Sydney, New South Wales, Australia, and her colleagues reported these findings in Blood.

“Multiple myeloma is a cancer that grows in bone, and, in most patients, it is associated with widespread bone loss and recurrent bone fractures, which can be extremely painful and debilitating,” Dr McDonald said.

“The current treatment for myeloma-associated bone disease with bisphosphonate drugs prevents further bone loss, but it doesn’t fix damaged bones, so patients continue to fracture. We wanted to re-stimulate bone formation and increase bone strength and resistance to fracture.”

So the researchers tested an antibody that targets and neutralizes sclerostin. In clinical studies of osteoporosis, such antibodies have been shown to increase bone mass and reduce fracture incidence.

In the mouse models of MM, the antibody prevented further bone loss and even doubled bone volume in some of the mice.

“When we looked at the bones before and after treatment, the difference was remarkable,” Dr McDonald said. “We saw less lesions or ‘holes’ in the bones after anti-sclerostin treatment. These lesions are the primary cause of bone pain, so this is an extremely important result.”

The treatment also made the bones substantially stronger, with more than double the resistance to fracture observed in many of the tests.

The researchers then combined the antibody with the bisphosphonate zoledronic acid and observed positive results.

“Bisphosphonates work by preventing bone breakdown, so we combined zoledronic acid with the new anti-sclerostin antibody that rebuilds bone,” Dr McDonald said. “Together, the impact on bone thickness, strength, and resistance to fracture was greater than either treatment alone.”

The researchers said these findings suggest a potential new strategy for reducing fractures in patients with MM.

“[M]yelomas, like other cancers, vary from individual to individual and can therefore be difficult to target,” said study author Peter I. Croucher, PhD, of the Garvan Institute of Medical Research.

“By targeting sclerostin, we are blocking a protein that is active in every person’s bones and not something unique to a person’s cancer. Therefore, in the future, when we test this antibody in humans, we are hopeful to see a response in most, if not all, patients.”

“We are now looking towards clinical trials for this antibody and, in the future, development of this type of therapy for the clinical treatment of multiple myeloma. This therapeutic approach has the potential to transform the prognosis for myeloma patients, enhancing quality of life, and ultimately reducing mortality. It also has clinical implications for the treatment of other cancers that develop in the skeleton.” 

Photo by Rhoda Baer

Narrow insurance plan coverage may prevent US cancer patients from receiving care at “high-quality” cancer centers, according to research published in the Journal of Clinical Oncology.

Researchers found that “narrow network” insurance plans—lower-premium plans with reduced access to certain providers—are more likely to exclude doctors associated with National Cancer Institute (NCI) and National Comprehensive Cancer Network (NCCN) cancer centers.

These centers are recognized for their scientific and research leadership, quality and safety initiatives, and access to expert physicians and clinical trials.

NCCN member institutions are particularly recognized for higher-quality care, and treatment at NCI-designated cancer centers is associated with lower mortality than other hospitals, particularly among more severely ill patients and those with more advanced disease.

For this study, researchers examined cancer provider networks offered on the 2014 individual health insurance exchanges and then determined which oncologists were affiliated with NCI-designated and NCCN cancer centers.

The researchers found that narrower networks were less likely to include physicians associated with NCI-designated and NCCN member institutions.

“To see such a robust result was surprising,” said study author Laura Yasaitis, PhD, of the University of Pennsylvania in Philadelphia.

“The finding that narrower networks were more likely to exclude NCI and NCCN oncologists was consistent no matter how we looked at it. This is not just a few networks. It’s a clear trend.”

The researchers said the results point to 2 major problems—transparency and access.

“Patients should be able to easily figure out whether the physicians they might need will be covered under a given plan,” said study author Justin E. Bekelman, MD, of the University of Pennsylvania.

The researchers suggested that insurers report doctor’s affiliations with NCI and NCCN cancer centers so that consumers can make more informed choices.

The team also suggested that insurers offer mechanisms that would allow patients to seek care out of network without incurring penalties in exceptional circumstances.

“If patients have narrow network plans and absolutely need the kind of complex cancer care that they can only receive from one of these providers, there should be a standard exception process to allow patients to access the care they need,” Dr Bekelman said. 

Photo by Rhoda Baer

Narrow insurance plan coverage may prevent US cancer patients from receiving care at “high-quality” cancer centers, according to research published in the Journal of Clinical Oncology.

Researchers found that “narrow network” insurance plans—lower-premium plans with reduced access to certain providers—are more likely to exclude doctors associated with National Cancer Institute (NCI) and National Comprehensive Cancer Network (NCCN) cancer centers.

These centers are recognized for their scientific and research leadership, quality and safety initiatives, and access to expert physicians and clinical trials.

NCCN member institutions are particularly recognized for higher-quality care, and treatment at NCI-designated cancer centers is associated with lower mortality than other hospitals, particularly among more severely ill patients and those with more advanced disease.

For this study, researchers examined cancer provider networks offered on the 2014 individual health insurance exchanges and then determined which oncologists were affiliated with NCI-designated and NCCN cancer centers.

The researchers found that narrower networks were less likely to include physicians associated with NCI-designated and NCCN member institutions.

“To see such a robust result was surprising,” said study author Laura Yasaitis, PhD, of the University of Pennsylvania in Philadelphia.

“The finding that narrower networks were more likely to exclude NCI and NCCN oncologists was consistent no matter how we looked at it. This is not just a few networks. It’s a clear trend.”

The researchers said the results point to 2 major problems—transparency and access.

“Patients should be able to easily figure out whether the physicians they might need will be covered under a given plan,” said study author Justin E. Bekelman, MD, of the University of Pennsylvania.

The researchers suggested that insurers report doctor’s affiliations with NCI and NCCN cancer centers so that consumers can make more informed choices.

The team also suggested that insurers offer mechanisms that would allow patients to seek care out of network without incurring penalties in exceptional circumstances.

“If patients have narrow network plans and absolutely need the kind of complex cancer care that they can only receive from one of these providers, there should be a standard exception process to allow patients to access the care they need,” Dr Bekelman said. 

Photo by Rhoda Baer

Narrow insurance plan coverage may prevent US cancer patients from receiving care at “high-quality” cancer centers, according to research published in the Journal of Clinical Oncology.

Researchers found that “narrow network” insurance plans—lower-premium plans with reduced access to certain providers—are more likely to exclude doctors associated with National Cancer Institute (NCI) and National Comprehensive Cancer Network (NCCN) cancer centers.

These centers are recognized for their scientific and research leadership, quality and safety initiatives, and access to expert physicians and clinical trials.

NCCN member institutions are particularly recognized for higher-quality care, and treatment at NCI-designated cancer centers is associated with lower mortality than other hospitals, particularly among more severely ill patients and those with more advanced disease.

For this study, researchers examined cancer provider networks offered on the 2014 individual health insurance exchanges and then determined which oncologists were affiliated with NCI-designated and NCCN cancer centers.

The researchers found that narrower networks were less likely to include physicians associated with NCI-designated and NCCN member institutions.

“To see such a robust result was surprising,” said study author Laura Yasaitis, PhD, of the University of Pennsylvania in Philadelphia.

“The finding that narrower networks were more likely to exclude NCI and NCCN oncologists was consistent no matter how we looked at it. This is not just a few networks. It’s a clear trend.”

The researchers said the results point to 2 major problems—transparency and access.

“Patients should be able to easily figure out whether the physicians they might need will be covered under a given plan,” said study author Justin E. Bekelman, MD, of the University of Pennsylvania.

The researchers suggested that insurers report doctor’s affiliations with NCI and NCCN cancer centers so that consumers can make more informed choices.

The team also suggested that insurers offer mechanisms that would allow patients to seek care out of network without incurring penalties in exceptional circumstances.

“If patients have narrow network plans and absolutely need the kind of complex cancer care that they can only receive from one of these providers, there should be a standard exception process to allow patients to access the care they need,” Dr Bekelman said.