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VSTs can treat 5 different viral infections after HSCT

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VSTs can treat 5 different viral infections after HSCT

College of Medicine
Ifigeneia Tzannou (left) and Bilal Omer Photo from Baylor

New research suggests virus-specific T cells (VSTs) can protect patients from severe viral infections that sometimes occur after hematopoietic stem cell transplant (HSCT).

The VSTs proved effective against 5 different viruses—Epstein-Barr virus (EBV), adenovirus (AdV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV-6).

Ifigeneia Tzannou, MD, of Baylor College of Medicine in Houston, Texas, and her colleagues reported these findings in the Journal of Clinical Oncology.

“In this study, we continued our previous work . . . in which we showed that patients who had developed an Epstein-Barr virus infection after a transplant . . . could be helped by receiving immune cells specialized in eliminating that particular virus,” Dr Tzannou said. “Then, we and others successfully targeted other viruses—namely, adenoviruses and cytomegalovirus.”

“The novel contribution of this study is that we have targeted additional viruses, the BK virus and the HHV-6 virus, which had not been targeted this way before,” added study author Bilal Omer, MD, of Baylor College of Medicine.

“This is important because the BK virus does not have an effective treatment, and the complications are significant, including severe pain and bleeding. These patients are in the hospital for weeks, months sometimes, and, now, we have a treatment option.”

The researchers tested their VSTs in a phase 2 trial of 38 HSCT recipients with at least 1 of the aforementioned viruses.

“[To prepare the VSTs,] we take blood from healthy donors who have already been exposed to these viruses and who we have confirmed have immune cells that can fight the infections,” Dr Tzannou said.

“We isolate the cells and let them multiply in culture. The final product is a mixture of cells that, together, can target all 5 viruses. We prepared 59 sets of virus-specific cells from different donors following this procedure.”

“Our strategy is to prepare a number of sets of virus-specific cells ahead of time and store them in a freezer, ready to use when a patient needs them,” Dr Omer noted. “To match patient and donor, we use elaborate matching algorithms.”

Patients

The trial included 38 patients who had undergone HSCT to treat acute myeloid leukemia/myelodysplastic syndromes (n=20), acute lymphoblastic leukemia (n=9), lymphoma/myeloma (n=3), or nonmalignant disorders (n=6).

These 38 patients had a total of 45 infections—CMV (n=17), EBV (n=2), AdV (n=7), BKV (n=16), and HHV-6 (n=3).

Response

The researchers monitored virus levels and other clinical responses in the 37 evaluable patients.

Six weeks after the first VST infusion, the overall response rate was 91.9%.

Seventeen patients received VSTs for persistent CMV. Sixteen of these patients (94.1%) responded, 6 with complete responses (CRs) and 10 with partial responses (PRs).

Two patients received VSTs for EBV, and both achieved a virologic CR.

Seven patients received VSTs for persistent AdV. The response rate was 71.4%. Four patients achieved a CR, 1 had a PR, and 2 patients did not respond.

Three patients received VSTs to treat HHV-6 reactivations. The response rate was 67%. Two patients had a PR, and 1 was not evaluable.

Sixteen patients received VSTs for BKV-associated hemorrhagic cystitis (n= 14) or BKV-associated nephritis (n=2).

All 16 patients responded. One had a clinical and virologic CR. Six had a clinical CR but a virologic PR. Seven had a virologic and clinical PR. And 2 patients had only a virologic PR.

A total of 15 patients received a second VST infusion—1 due to lack of response, 7 who had a PR, and 7 due to recurrence. Ten of these patients responded to the second infusion—1 with a CR and 9 with a PR.

 

 

Four patients received a third infusion of VSTs. Two achieved a CR, 1 had a PR, and 1 did not respond.

Toxicity

One patient developed an isolated fever within 24 hours of VST infusion, but the researchers did not observe any other immediate toxicities.

One of the patients with BKV-associated hemorrhagic cystitis experienced transient hydronephrosis and a decrease in renal function associated with a concomitant bacterial urinary tract infection.

Nineteen patients had prior grade 2 to 4 graft-versus-host disease (GVHD)—15 with grade 2 and 4 with grade 3. All GVHD was quiescent at the time of VST infusion.

One patient developed recurrent grade 3 gastrointestinal GVHD after VST infusion and rapid corticosteroid taper. Five patients developed recurrent (n=3) or de novo (n=2) grade 1 to 2 skin GVHD, which resolved with topical treatment (n=4) and reinitiation of corticosteroid treatment (n=1).

Two patients had a flare of upper-gastrointestinal GVHD, which resolved after a brief corticosteroid course.

“We didn’t have any significant toxicities,” Dr Tzannou said. “Taken together, the results of this trial suggest that it is reasonable to consider this treatment as an early option for these patients. We hope that the results of a future multicenter, phase 3 clinical trial will help raise awareness in both physicians and patients that this treatment, which is safe and effective, is available.”

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College of Medicine
Ifigeneia Tzannou (left) and Bilal Omer Photo from Baylor

New research suggests virus-specific T cells (VSTs) can protect patients from severe viral infections that sometimes occur after hematopoietic stem cell transplant (HSCT).

The VSTs proved effective against 5 different viruses—Epstein-Barr virus (EBV), adenovirus (AdV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV-6).

Ifigeneia Tzannou, MD, of Baylor College of Medicine in Houston, Texas, and her colleagues reported these findings in the Journal of Clinical Oncology.

“In this study, we continued our previous work . . . in which we showed that patients who had developed an Epstein-Barr virus infection after a transplant . . . could be helped by receiving immune cells specialized in eliminating that particular virus,” Dr Tzannou said. “Then, we and others successfully targeted other viruses—namely, adenoviruses and cytomegalovirus.”

“The novel contribution of this study is that we have targeted additional viruses, the BK virus and the HHV-6 virus, which had not been targeted this way before,” added study author Bilal Omer, MD, of Baylor College of Medicine.

“This is important because the BK virus does not have an effective treatment, and the complications are significant, including severe pain and bleeding. These patients are in the hospital for weeks, months sometimes, and, now, we have a treatment option.”

The researchers tested their VSTs in a phase 2 trial of 38 HSCT recipients with at least 1 of the aforementioned viruses.

“[To prepare the VSTs,] we take blood from healthy donors who have already been exposed to these viruses and who we have confirmed have immune cells that can fight the infections,” Dr Tzannou said.

“We isolate the cells and let them multiply in culture. The final product is a mixture of cells that, together, can target all 5 viruses. We prepared 59 sets of virus-specific cells from different donors following this procedure.”

“Our strategy is to prepare a number of sets of virus-specific cells ahead of time and store them in a freezer, ready to use when a patient needs them,” Dr Omer noted. “To match patient and donor, we use elaborate matching algorithms.”

Patients

The trial included 38 patients who had undergone HSCT to treat acute myeloid leukemia/myelodysplastic syndromes (n=20), acute lymphoblastic leukemia (n=9), lymphoma/myeloma (n=3), or nonmalignant disorders (n=6).

These 38 patients had a total of 45 infections—CMV (n=17), EBV (n=2), AdV (n=7), BKV (n=16), and HHV-6 (n=3).

Response

The researchers monitored virus levels and other clinical responses in the 37 evaluable patients.

Six weeks after the first VST infusion, the overall response rate was 91.9%.

Seventeen patients received VSTs for persistent CMV. Sixteen of these patients (94.1%) responded, 6 with complete responses (CRs) and 10 with partial responses (PRs).

Two patients received VSTs for EBV, and both achieved a virologic CR.

Seven patients received VSTs for persistent AdV. The response rate was 71.4%. Four patients achieved a CR, 1 had a PR, and 2 patients did not respond.

Three patients received VSTs to treat HHV-6 reactivations. The response rate was 67%. Two patients had a PR, and 1 was not evaluable.

Sixteen patients received VSTs for BKV-associated hemorrhagic cystitis (n= 14) or BKV-associated nephritis (n=2).

All 16 patients responded. One had a clinical and virologic CR. Six had a clinical CR but a virologic PR. Seven had a virologic and clinical PR. And 2 patients had only a virologic PR.

A total of 15 patients received a second VST infusion—1 due to lack of response, 7 who had a PR, and 7 due to recurrence. Ten of these patients responded to the second infusion—1 with a CR and 9 with a PR.

 

 

Four patients received a third infusion of VSTs. Two achieved a CR, 1 had a PR, and 1 did not respond.

Toxicity

One patient developed an isolated fever within 24 hours of VST infusion, but the researchers did not observe any other immediate toxicities.

One of the patients with BKV-associated hemorrhagic cystitis experienced transient hydronephrosis and a decrease in renal function associated with a concomitant bacterial urinary tract infection.

Nineteen patients had prior grade 2 to 4 graft-versus-host disease (GVHD)—15 with grade 2 and 4 with grade 3. All GVHD was quiescent at the time of VST infusion.

One patient developed recurrent grade 3 gastrointestinal GVHD after VST infusion and rapid corticosteroid taper. Five patients developed recurrent (n=3) or de novo (n=2) grade 1 to 2 skin GVHD, which resolved with topical treatment (n=4) and reinitiation of corticosteroid treatment (n=1).

Two patients had a flare of upper-gastrointestinal GVHD, which resolved after a brief corticosteroid course.

“We didn’t have any significant toxicities,” Dr Tzannou said. “Taken together, the results of this trial suggest that it is reasonable to consider this treatment as an early option for these patients. We hope that the results of a future multicenter, phase 3 clinical trial will help raise awareness in both physicians and patients that this treatment, which is safe and effective, is available.”

College of Medicine
Ifigeneia Tzannou (left) and Bilal Omer Photo from Baylor

New research suggests virus-specific T cells (VSTs) can protect patients from severe viral infections that sometimes occur after hematopoietic stem cell transplant (HSCT).

The VSTs proved effective against 5 different viruses—Epstein-Barr virus (EBV), adenovirus (AdV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV-6).

Ifigeneia Tzannou, MD, of Baylor College of Medicine in Houston, Texas, and her colleagues reported these findings in the Journal of Clinical Oncology.

“In this study, we continued our previous work . . . in which we showed that patients who had developed an Epstein-Barr virus infection after a transplant . . . could be helped by receiving immune cells specialized in eliminating that particular virus,” Dr Tzannou said. “Then, we and others successfully targeted other viruses—namely, adenoviruses and cytomegalovirus.”

“The novel contribution of this study is that we have targeted additional viruses, the BK virus and the HHV-6 virus, which had not been targeted this way before,” added study author Bilal Omer, MD, of Baylor College of Medicine.

“This is important because the BK virus does not have an effective treatment, and the complications are significant, including severe pain and bleeding. These patients are in the hospital for weeks, months sometimes, and, now, we have a treatment option.”

The researchers tested their VSTs in a phase 2 trial of 38 HSCT recipients with at least 1 of the aforementioned viruses.

“[To prepare the VSTs,] we take blood from healthy donors who have already been exposed to these viruses and who we have confirmed have immune cells that can fight the infections,” Dr Tzannou said.

“We isolate the cells and let them multiply in culture. The final product is a mixture of cells that, together, can target all 5 viruses. We prepared 59 sets of virus-specific cells from different donors following this procedure.”

“Our strategy is to prepare a number of sets of virus-specific cells ahead of time and store them in a freezer, ready to use when a patient needs them,” Dr Omer noted. “To match patient and donor, we use elaborate matching algorithms.”

Patients

The trial included 38 patients who had undergone HSCT to treat acute myeloid leukemia/myelodysplastic syndromes (n=20), acute lymphoblastic leukemia (n=9), lymphoma/myeloma (n=3), or nonmalignant disorders (n=6).

These 38 patients had a total of 45 infections—CMV (n=17), EBV (n=2), AdV (n=7), BKV (n=16), and HHV-6 (n=3).

Response

The researchers monitored virus levels and other clinical responses in the 37 evaluable patients.

Six weeks after the first VST infusion, the overall response rate was 91.9%.

Seventeen patients received VSTs for persistent CMV. Sixteen of these patients (94.1%) responded, 6 with complete responses (CRs) and 10 with partial responses (PRs).

Two patients received VSTs for EBV, and both achieved a virologic CR.

Seven patients received VSTs for persistent AdV. The response rate was 71.4%. Four patients achieved a CR, 1 had a PR, and 2 patients did not respond.

Three patients received VSTs to treat HHV-6 reactivations. The response rate was 67%. Two patients had a PR, and 1 was not evaluable.

Sixteen patients received VSTs for BKV-associated hemorrhagic cystitis (n= 14) or BKV-associated nephritis (n=2).

All 16 patients responded. One had a clinical and virologic CR. Six had a clinical CR but a virologic PR. Seven had a virologic and clinical PR. And 2 patients had only a virologic PR.

A total of 15 patients received a second VST infusion—1 due to lack of response, 7 who had a PR, and 7 due to recurrence. Ten of these patients responded to the second infusion—1 with a CR and 9 with a PR.

 

 

Four patients received a third infusion of VSTs. Two achieved a CR, 1 had a PR, and 1 did not respond.

Toxicity

One patient developed an isolated fever within 24 hours of VST infusion, but the researchers did not observe any other immediate toxicities.

One of the patients with BKV-associated hemorrhagic cystitis experienced transient hydronephrosis and a decrease in renal function associated with a concomitant bacterial urinary tract infection.

Nineteen patients had prior grade 2 to 4 graft-versus-host disease (GVHD)—15 with grade 2 and 4 with grade 3. All GVHD was quiescent at the time of VST infusion.

One patient developed recurrent grade 3 gastrointestinal GVHD after VST infusion and rapid corticosteroid taper. Five patients developed recurrent (n=3) or de novo (n=2) grade 1 to 2 skin GVHD, which resolved with topical treatment (n=4) and reinitiation of corticosteroid treatment (n=1).

Two patients had a flare of upper-gastrointestinal GVHD, which resolved after a brief corticosteroid course.

“We didn’t have any significant toxicities,” Dr Tzannou said. “Taken together, the results of this trial suggest that it is reasonable to consider this treatment as an early option for these patients. We hope that the results of a future multicenter, phase 3 clinical trial will help raise awareness in both physicians and patients that this treatment, which is safe and effective, is available.”

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Researchers find higher opioid use among cancer survivors

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Prescription drugs

A study of residents in Ontario, Canada, showed that opioid prescription use was more common in cancer survivors than in individuals without a history of cancer.

This was true even among survivors who were 10 or more years past their cancer diagnosis.

Rinku Sutradhar, PhD, of the University of Toronto in Ontario, Canada, and her colleagues reported these findings in Cancer.

The researchers said little is known about prescribing opioids to relieve pain in individuals who have survived cancer.

To investigate, the team looked at opioid prescribing among residents of Ontario, Canada, with and without a history of cancer.

The study included 8601 adults who were at least 5 years past a cancer diagnosis. These subjects were were matched with 8601 individuals without a prior cancer diagnosis. The subjects were matched based on sex and calendar year of birth.

The researchers looked for opioid prescriptions filled at a pharmacy during the observation period. Follow-up was stopped at any indication of cancer recurrence, second malignancy, or new cancer diagnosis.

The rate of opioid prescribing was 1.22 times higher among cancer survivors than corresponding matched controls.

Over a 36-month period, the average number of opioid prescriptions filled by cancer survivors was 7.7, compared with 6.3 for controls.

This increased rate of opioid prescribing was also seen among survivors who were 10 or more years past their cancer diagnosis.

Individuals with lower income and those who were younger, from rural neighborhoods, and with more comorbidities had significantly higher prescribing rates. Sex was not associated with prescribing rates.

“Our research findings raise concerns about the diagnosis and management of chronic pain problems among survivors stemming from their cancer diagnosis or treatment,” Dr Sutradhar said. “Physicians providing primary care to cancer survivors should consider close examination of reasons for continued opioid use to differentiate chronic pain from dependency.”

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Photo courtesy of the CDC
Prescription drugs

A study of residents in Ontario, Canada, showed that opioid prescription use was more common in cancer survivors than in individuals without a history of cancer.

This was true even among survivors who were 10 or more years past their cancer diagnosis.

Rinku Sutradhar, PhD, of the University of Toronto in Ontario, Canada, and her colleagues reported these findings in Cancer.

The researchers said little is known about prescribing opioids to relieve pain in individuals who have survived cancer.

To investigate, the team looked at opioid prescribing among residents of Ontario, Canada, with and without a history of cancer.

The study included 8601 adults who were at least 5 years past a cancer diagnosis. These subjects were were matched with 8601 individuals without a prior cancer diagnosis. The subjects were matched based on sex and calendar year of birth.

The researchers looked for opioid prescriptions filled at a pharmacy during the observation period. Follow-up was stopped at any indication of cancer recurrence, second malignancy, or new cancer diagnosis.

The rate of opioid prescribing was 1.22 times higher among cancer survivors than corresponding matched controls.

Over a 36-month period, the average number of opioid prescriptions filled by cancer survivors was 7.7, compared with 6.3 for controls.

This increased rate of opioid prescribing was also seen among survivors who were 10 or more years past their cancer diagnosis.

Individuals with lower income and those who were younger, from rural neighborhoods, and with more comorbidities had significantly higher prescribing rates. Sex was not associated with prescribing rates.

“Our research findings raise concerns about the diagnosis and management of chronic pain problems among survivors stemming from their cancer diagnosis or treatment,” Dr Sutradhar said. “Physicians providing primary care to cancer survivors should consider close examination of reasons for continued opioid use to differentiate chronic pain from dependency.”

Photo courtesy of the CDC
Prescription drugs

A study of residents in Ontario, Canada, showed that opioid prescription use was more common in cancer survivors than in individuals without a history of cancer.

This was true even among survivors who were 10 or more years past their cancer diagnosis.

Rinku Sutradhar, PhD, of the University of Toronto in Ontario, Canada, and her colleagues reported these findings in Cancer.

The researchers said little is known about prescribing opioids to relieve pain in individuals who have survived cancer.

To investigate, the team looked at opioid prescribing among residents of Ontario, Canada, with and without a history of cancer.

The study included 8601 adults who were at least 5 years past a cancer diagnosis. These subjects were were matched with 8601 individuals without a prior cancer diagnosis. The subjects were matched based on sex and calendar year of birth.

The researchers looked for opioid prescriptions filled at a pharmacy during the observation period. Follow-up was stopped at any indication of cancer recurrence, second malignancy, or new cancer diagnosis.

The rate of opioid prescribing was 1.22 times higher among cancer survivors than corresponding matched controls.

Over a 36-month period, the average number of opioid prescriptions filled by cancer survivors was 7.7, compared with 6.3 for controls.

This increased rate of opioid prescribing was also seen among survivors who were 10 or more years past their cancer diagnosis.

Individuals with lower income and those who were younger, from rural neighborhoods, and with more comorbidities had significantly higher prescribing rates. Sex was not associated with prescribing rates.

“Our research findings raise concerns about the diagnosis and management of chronic pain problems among survivors stemming from their cancer diagnosis or treatment,” Dr Sutradhar said. “Physicians providing primary care to cancer survivors should consider close examination of reasons for continued opioid use to differentiate chronic pain from dependency.”

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Tests can produce confusing results after HSCT in MM

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Micrograph showing MM

Tests used to assess treatment response in multiple myeloma (MM) may often produce confusing results after patients have undergone hematopoietic stem cell transplant (HSCT), a new study suggests.

The tests—serum protein electrophoresis/serum immunofixation electrophoresis (SPEP/SIFE) and serum free light chain assay (SFLCA)—can sometimes produce an oligoclonal pattern that can be mistaken for an M spike and suggest disease recurrence.

The study showed that this confusing result was significantly more likely to occur after patients underwent HSCT than after they received chemotherapy.

Gurmukh Singh, MD, PhD, of Augusta University in Augusta, Georgia, reported these findings in the Journal of Clinical Medicine Research.

For this study, Dr Singh looked at lab and clinical data on 251 MM patients treated from January 2010 to December 2016. One hundred and fifty-nine of those patients received autologous HSCTs.

Dr Singh compared results of SPEP/SIFE and/or SFLCA in patients who underwent HSCT and patients who did not. Each patient had at least 3 tests, and, for HSCT recipients, at least 2 of the tests occurred after transplant.

The incidence of oligoclonal patterns was significantly higher in HSCT recipients than in patients who had chemotherapy alone—57.9% and 8.8%, respectively (P=0.000003).

Only 5 of the 159 HSCT recipients had an oligoclonal pattern before treatment, but 92 of them had one afterward.

More than half of the oligoclonal patterns developed within the first year of HSCT. The earliest pattern was detected at 2 months—as soon as the first post-transplant tests were done—and a few occurred as late as 5 years later.

“We want to emphasize that oligoclonal bands should mostly be recognized as a response to treatment and not be mistaken as a recurrence of the original tumor,” Dr Singh said.

He explained that the key clarifier appears to be the location of the M spike when the diagnosis is made compared to the location of new spikes that may show up after HSCT.

“If the original peak was at location A, now the peak is location B, that allows us to determine that it is not the same abnormal, malignant antibody,” he said. “If it’s in a different location, it’s not the same protein. [T]his is just a normal response of recovery of the bone marrow that could be mistaken for recurrence of the disease.”

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Micrograph showing MM

Tests used to assess treatment response in multiple myeloma (MM) may often produce confusing results after patients have undergone hematopoietic stem cell transplant (HSCT), a new study suggests.

The tests—serum protein electrophoresis/serum immunofixation electrophoresis (SPEP/SIFE) and serum free light chain assay (SFLCA)—can sometimes produce an oligoclonal pattern that can be mistaken for an M spike and suggest disease recurrence.

The study showed that this confusing result was significantly more likely to occur after patients underwent HSCT than after they received chemotherapy.

Gurmukh Singh, MD, PhD, of Augusta University in Augusta, Georgia, reported these findings in the Journal of Clinical Medicine Research.

For this study, Dr Singh looked at lab and clinical data on 251 MM patients treated from January 2010 to December 2016. One hundred and fifty-nine of those patients received autologous HSCTs.

Dr Singh compared results of SPEP/SIFE and/or SFLCA in patients who underwent HSCT and patients who did not. Each patient had at least 3 tests, and, for HSCT recipients, at least 2 of the tests occurred after transplant.

The incidence of oligoclonal patterns was significantly higher in HSCT recipients than in patients who had chemotherapy alone—57.9% and 8.8%, respectively (P=0.000003).

Only 5 of the 159 HSCT recipients had an oligoclonal pattern before treatment, but 92 of them had one afterward.

More than half of the oligoclonal patterns developed within the first year of HSCT. The earliest pattern was detected at 2 months—as soon as the first post-transplant tests were done—and a few occurred as late as 5 years later.

“We want to emphasize that oligoclonal bands should mostly be recognized as a response to treatment and not be mistaken as a recurrence of the original tumor,” Dr Singh said.

He explained that the key clarifier appears to be the location of the M spike when the diagnosis is made compared to the location of new spikes that may show up after HSCT.

“If the original peak was at location A, now the peak is location B, that allows us to determine that it is not the same abnormal, malignant antibody,” he said. “If it’s in a different location, it’s not the same protein. [T]his is just a normal response of recovery of the bone marrow that could be mistaken for recurrence of the disease.”

Micrograph showing MM

Tests used to assess treatment response in multiple myeloma (MM) may often produce confusing results after patients have undergone hematopoietic stem cell transplant (HSCT), a new study suggests.

The tests—serum protein electrophoresis/serum immunofixation electrophoresis (SPEP/SIFE) and serum free light chain assay (SFLCA)—can sometimes produce an oligoclonal pattern that can be mistaken for an M spike and suggest disease recurrence.

The study showed that this confusing result was significantly more likely to occur after patients underwent HSCT than after they received chemotherapy.

Gurmukh Singh, MD, PhD, of Augusta University in Augusta, Georgia, reported these findings in the Journal of Clinical Medicine Research.

For this study, Dr Singh looked at lab and clinical data on 251 MM patients treated from January 2010 to December 2016. One hundred and fifty-nine of those patients received autologous HSCTs.

Dr Singh compared results of SPEP/SIFE and/or SFLCA in patients who underwent HSCT and patients who did not. Each patient had at least 3 tests, and, for HSCT recipients, at least 2 of the tests occurred after transplant.

The incidence of oligoclonal patterns was significantly higher in HSCT recipients than in patients who had chemotherapy alone—57.9% and 8.8%, respectively (P=0.000003).

Only 5 of the 159 HSCT recipients had an oligoclonal pattern before treatment, but 92 of them had one afterward.

More than half of the oligoclonal patterns developed within the first year of HSCT. The earliest pattern was detected at 2 months—as soon as the first post-transplant tests were done—and a few occurred as late as 5 years later.

“We want to emphasize that oligoclonal bands should mostly be recognized as a response to treatment and not be mistaken as a recurrence of the original tumor,” Dr Singh said.

He explained that the key clarifier appears to be the location of the M spike when the diagnosis is made compared to the location of new spikes that may show up after HSCT.

“If the original peak was at location A, now the peak is location B, that allows us to determine that it is not the same abnormal, malignant antibody,” he said. “If it’s in a different location, it’s not the same protein. [T]his is just a normal response of recovery of the bone marrow that could be mistaken for recurrence of the disease.”

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Insured cancer patients report ‘overwhelming’ financial distress

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Cancer patient receiving chemotherapy

A study of 300 US cancer patients showed that paying for care can cause “overwhelming” financial distress, even when patients have health insurance.

Sixteen percent of the patients studied reported “high or overwhelming” financial distress, spending a median of 31% of their monthly household income on healthcare, not including insurance premiums.

They had a median monthly out-of-pocket cost of $728 (range, $6 to $47,250).

Fumiko Chino, MD, of Duke University Medical Center in Durham, North Carolina, and her colleagues reported these findings in a letter to JAMA Oncology.

The researchers interviewed 300 insured cancer patients for this study. They had a median age of 59.6, and 68.3% were married.

Fifty-six percent of patients had private insurance, 35.7% had Medicare, and 7.3% had Medicaid.

Annual household incomes were as follows:

  • 45.7%, $60,000 or greater
  • 15.7%, $40,000 to $59,999
  • 17.7%, $20,000 to 39,999
  • 13.7%, lower than $20,000
  • 7.3%, unknown.

The median monthly out-of-pocket cost for care was $592 (range, $3-$47,250), not including insurance premiums. The median relative cost of care was 11% of a patient’s monthly household income.

“Those who spend more than 10% of their income on healthcare costs are considered underinsured,” Dr Chino said. “Learning about the cost-sharing burden on some insured patients is important right now, given the uncertainty in health insurance.”

Most of the patients studied (83.7%, n=251) reported no, low, or average financial distress. Their median relative cost of care was 10% of their monthly household income, and their median monthly out-of-pocket cost was $565 (range, $3 to $26,756). Six percent of these patients had Medicaid, 39% had Medicare, and 53.8% had private insurance.

For the 16.3% of patients (n=49) who reported high or overwhelming financial distress, 67.3% had private insurance, 18.4% had Medicare, and 14.3% had Medicaid. As stated above, their median relative cost of care was 31% of their monthly household income, and their median monthly out-of-pocket cost was $728 (range, $6 to $47,250).

“This study adds to the growing evidence that we need to intervene,” said study author Yousuf Zafar, MD, of Duke Cancer Institute.

“We know there are a lot of barriers that prevent patients from talking about cost with their providers. We need to create tools for patients at risk of financial toxicity and connect them with resources in a timely fashion so they can afford their care.”

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Photo by Rhoda Baer
Cancer patient receiving chemotherapy

A study of 300 US cancer patients showed that paying for care can cause “overwhelming” financial distress, even when patients have health insurance.

Sixteen percent of the patients studied reported “high or overwhelming” financial distress, spending a median of 31% of their monthly household income on healthcare, not including insurance premiums.

They had a median monthly out-of-pocket cost of $728 (range, $6 to $47,250).

Fumiko Chino, MD, of Duke University Medical Center in Durham, North Carolina, and her colleagues reported these findings in a letter to JAMA Oncology.

The researchers interviewed 300 insured cancer patients for this study. They had a median age of 59.6, and 68.3% were married.

Fifty-six percent of patients had private insurance, 35.7% had Medicare, and 7.3% had Medicaid.

Annual household incomes were as follows:

  • 45.7%, $60,000 or greater
  • 15.7%, $40,000 to $59,999
  • 17.7%, $20,000 to 39,999
  • 13.7%, lower than $20,000
  • 7.3%, unknown.

The median monthly out-of-pocket cost for care was $592 (range, $3-$47,250), not including insurance premiums. The median relative cost of care was 11% of a patient’s monthly household income.

“Those who spend more than 10% of their income on healthcare costs are considered underinsured,” Dr Chino said. “Learning about the cost-sharing burden on some insured patients is important right now, given the uncertainty in health insurance.”

Most of the patients studied (83.7%, n=251) reported no, low, or average financial distress. Their median relative cost of care was 10% of their monthly household income, and their median monthly out-of-pocket cost was $565 (range, $3 to $26,756). Six percent of these patients had Medicaid, 39% had Medicare, and 53.8% had private insurance.

For the 16.3% of patients (n=49) who reported high or overwhelming financial distress, 67.3% had private insurance, 18.4% had Medicare, and 14.3% had Medicaid. As stated above, their median relative cost of care was 31% of their monthly household income, and their median monthly out-of-pocket cost was $728 (range, $6 to $47,250).

“This study adds to the growing evidence that we need to intervene,” said study author Yousuf Zafar, MD, of Duke Cancer Institute.

“We know there are a lot of barriers that prevent patients from talking about cost with their providers. We need to create tools for patients at risk of financial toxicity and connect them with resources in a timely fashion so they can afford their care.”

Photo by Rhoda Baer
Cancer patient receiving chemotherapy

A study of 300 US cancer patients showed that paying for care can cause “overwhelming” financial distress, even when patients have health insurance.

Sixteen percent of the patients studied reported “high or overwhelming” financial distress, spending a median of 31% of their monthly household income on healthcare, not including insurance premiums.

They had a median monthly out-of-pocket cost of $728 (range, $6 to $47,250).

Fumiko Chino, MD, of Duke University Medical Center in Durham, North Carolina, and her colleagues reported these findings in a letter to JAMA Oncology.

The researchers interviewed 300 insured cancer patients for this study. They had a median age of 59.6, and 68.3% were married.

Fifty-six percent of patients had private insurance, 35.7% had Medicare, and 7.3% had Medicaid.

Annual household incomes were as follows:

  • 45.7%, $60,000 or greater
  • 15.7%, $40,000 to $59,999
  • 17.7%, $20,000 to 39,999
  • 13.7%, lower than $20,000
  • 7.3%, unknown.

The median monthly out-of-pocket cost for care was $592 (range, $3-$47,250), not including insurance premiums. The median relative cost of care was 11% of a patient’s monthly household income.

“Those who spend more than 10% of their income on healthcare costs are considered underinsured,” Dr Chino said. “Learning about the cost-sharing burden on some insured patients is important right now, given the uncertainty in health insurance.”

Most of the patients studied (83.7%, n=251) reported no, low, or average financial distress. Their median relative cost of care was 10% of their monthly household income, and their median monthly out-of-pocket cost was $565 (range, $3 to $26,756). Six percent of these patients had Medicaid, 39% had Medicare, and 53.8% had private insurance.

For the 16.3% of patients (n=49) who reported high or overwhelming financial distress, 67.3% had private insurance, 18.4% had Medicare, and 14.3% had Medicaid. As stated above, their median relative cost of care was 31% of their monthly household income, and their median monthly out-of-pocket cost was $728 (range, $6 to $47,250).

“This study adds to the growing evidence that we need to intervene,” said study author Yousuf Zafar, MD, of Duke Cancer Institute.

“We know there are a lot of barriers that prevent patients from talking about cost with their providers. We need to create tools for patients at risk of financial toxicity and connect them with resources in a timely fashion so they can afford their care.”

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Advanced cancer patients have lower survival after cardiac arrest

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A new study suggests patients with advanced cancer who suffer cardiac arrest in the hospital have a survival rate of less than 10%, which is about half the rate of patients without cancer who suffer cardiac arrest.

This finding helps to clear up some myths about cardiac arrest survival and can be used as a guidepost when hospitalized cancer patients and their families consider do-not-resuscitate (DNR) orders, said Jeffrey T. Bruckel, MD, of the University of Rochester Medical Center in New York.

“We’re hopeful that our study, in some way, will help doctors and cancer patients make more informed decisions about the end of life,” Dr Bruckel said. “It’s very important to have early, frank discussions around the goals of care.”

Dr Bruckel and his colleagues published their study in the Journal of Oncology Practice.

The researchers used a US-wide resuscitation registry to evaluate survival after cardiac arrest in patients treated at 369 hospitals.

The study excluded patients with implantable defibrillators and those who were admitted for surgery, emergency room treatment, rehabilitation, or treatment from cardiac catheterization labs or interventional radiology.

Of the 47,157 eligible patients who experienced cardiac arrest, 14% (n=6585) had advanced cancer, including hematologic malignancies.

After cardiac arrest, 57.5% of the advanced cancer patients were resuscitated successfully, as were 63% of non-cancer patients (P<0.001).

After resuscitation, 9.6% of the cancer patients survived to be discharged, compared to 19.2% of non-cancer patients (P<0.001).

When the researchers adjusted their analysis for potential confounders, results were similar. The rate of successful resuscitation was 52.3% in advanced cancer patients and 56.6% in non-cancer patients (P<0.001). The rate of survival to discharge was 7.4% and 13.4%, respectively (P<0.001).

Dr Bruckel said there was no evidence to suggest that patients with advanced cancer received less aggressive resuscitation care.

However, there was a significant difference in the mean duration of resuscitation time among non-survivors with cancer—22.5 minutes—and non-survivors without cancer—24.2 minutes (P<0.001). After adjustment, the mean duration of resuscitation was 22.5 minutes and 24.1 minutes, respectively (P<0.001).

Cancer patients were more likely than those without cancer to sign DNR orders after resuscitation—55.6% and 43%, respectively (P<0.001). Results were similar after adjustment—50.4% and 41.6%, respectively (P<0.001).

Dr Bruckel and his colleagues said there were several limitations to this study, including a lack of detailed data on the types of advanced cancer and cancer treatments being given at the time of cardiac arrest.

Therefore, the next step in advancing this work is to gather data on the types of cancer diagnosis and treatment plans of patients who undergo in-hospital cardiac arrest.

Dr Bruckel also believes it is important to know how patients feel about this data and how both patients and physicians are using this data in decision-making.

“A large component of end-of-life care involves patient and family care decision-making, and a lot of that is driven by the routine discussions that we have,” Dr Bruckel said. “Not every patient is going to want detailed information, but for those that do, it’s important to have it. It’s important to tell them what we know.” 

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Photo by Diane Reid
Hospital room

A new study suggests patients with advanced cancer who suffer cardiac arrest in the hospital have a survival rate of less than 10%, which is about half the rate of patients without cancer who suffer cardiac arrest.

This finding helps to clear up some myths about cardiac arrest survival and can be used as a guidepost when hospitalized cancer patients and their families consider do-not-resuscitate (DNR) orders, said Jeffrey T. Bruckel, MD, of the University of Rochester Medical Center in New York.

“We’re hopeful that our study, in some way, will help doctors and cancer patients make more informed decisions about the end of life,” Dr Bruckel said. “It’s very important to have early, frank discussions around the goals of care.”

Dr Bruckel and his colleagues published their study in the Journal of Oncology Practice.

The researchers used a US-wide resuscitation registry to evaluate survival after cardiac arrest in patients treated at 369 hospitals.

The study excluded patients with implantable defibrillators and those who were admitted for surgery, emergency room treatment, rehabilitation, or treatment from cardiac catheterization labs or interventional radiology.

Of the 47,157 eligible patients who experienced cardiac arrest, 14% (n=6585) had advanced cancer, including hematologic malignancies.

After cardiac arrest, 57.5% of the advanced cancer patients were resuscitated successfully, as were 63% of non-cancer patients (P<0.001).

After resuscitation, 9.6% of the cancer patients survived to be discharged, compared to 19.2% of non-cancer patients (P<0.001).

When the researchers adjusted their analysis for potential confounders, results were similar. The rate of successful resuscitation was 52.3% in advanced cancer patients and 56.6% in non-cancer patients (P<0.001). The rate of survival to discharge was 7.4% and 13.4%, respectively (P<0.001).

Dr Bruckel said there was no evidence to suggest that patients with advanced cancer received less aggressive resuscitation care.

However, there was a significant difference in the mean duration of resuscitation time among non-survivors with cancer—22.5 minutes—and non-survivors without cancer—24.2 minutes (P<0.001). After adjustment, the mean duration of resuscitation was 22.5 minutes and 24.1 minutes, respectively (P<0.001).

Cancer patients were more likely than those without cancer to sign DNR orders after resuscitation—55.6% and 43%, respectively (P<0.001). Results were similar after adjustment—50.4% and 41.6%, respectively (P<0.001).

Dr Bruckel and his colleagues said there were several limitations to this study, including a lack of detailed data on the types of advanced cancer and cancer treatments being given at the time of cardiac arrest.

Therefore, the next step in advancing this work is to gather data on the types of cancer diagnosis and treatment plans of patients who undergo in-hospital cardiac arrest.

Dr Bruckel also believes it is important to know how patients feel about this data and how both patients and physicians are using this data in decision-making.

“A large component of end-of-life care involves patient and family care decision-making, and a lot of that is driven by the routine discussions that we have,” Dr Bruckel said. “Not every patient is going to want detailed information, but for those that do, it’s important to have it. It’s important to tell them what we know.” 

Photo by Diane Reid
Hospital room

A new study suggests patients with advanced cancer who suffer cardiac arrest in the hospital have a survival rate of less than 10%, which is about half the rate of patients without cancer who suffer cardiac arrest.

This finding helps to clear up some myths about cardiac arrest survival and can be used as a guidepost when hospitalized cancer patients and their families consider do-not-resuscitate (DNR) orders, said Jeffrey T. Bruckel, MD, of the University of Rochester Medical Center in New York.

“We’re hopeful that our study, in some way, will help doctors and cancer patients make more informed decisions about the end of life,” Dr Bruckel said. “It’s very important to have early, frank discussions around the goals of care.”

Dr Bruckel and his colleagues published their study in the Journal of Oncology Practice.

The researchers used a US-wide resuscitation registry to evaluate survival after cardiac arrest in patients treated at 369 hospitals.

The study excluded patients with implantable defibrillators and those who were admitted for surgery, emergency room treatment, rehabilitation, or treatment from cardiac catheterization labs or interventional radiology.

Of the 47,157 eligible patients who experienced cardiac arrest, 14% (n=6585) had advanced cancer, including hematologic malignancies.

After cardiac arrest, 57.5% of the advanced cancer patients were resuscitated successfully, as were 63% of non-cancer patients (P<0.001).

After resuscitation, 9.6% of the cancer patients survived to be discharged, compared to 19.2% of non-cancer patients (P<0.001).

When the researchers adjusted their analysis for potential confounders, results were similar. The rate of successful resuscitation was 52.3% in advanced cancer patients and 56.6% in non-cancer patients (P<0.001). The rate of survival to discharge was 7.4% and 13.4%, respectively (P<0.001).

Dr Bruckel said there was no evidence to suggest that patients with advanced cancer received less aggressive resuscitation care.

However, there was a significant difference in the mean duration of resuscitation time among non-survivors with cancer—22.5 minutes—and non-survivors without cancer—24.2 minutes (P<0.001). After adjustment, the mean duration of resuscitation was 22.5 minutes and 24.1 minutes, respectively (P<0.001).

Cancer patients were more likely than those without cancer to sign DNR orders after resuscitation—55.6% and 43%, respectively (P<0.001). Results were similar after adjustment—50.4% and 41.6%, respectively (P<0.001).

Dr Bruckel and his colleagues said there were several limitations to this study, including a lack of detailed data on the types of advanced cancer and cancer treatments being given at the time of cardiac arrest.

Therefore, the next step in advancing this work is to gather data on the types of cancer diagnosis and treatment plans of patients who undergo in-hospital cardiac arrest.

Dr Bruckel also believes it is important to know how patients feel about this data and how both patients and physicians are using this data in decision-making.

“A large component of end-of-life care involves patient and family care decision-making, and a lot of that is driven by the routine discussions that we have,” Dr Bruckel said. “Not every patient is going to want detailed information, but for those that do, it’s important to have it. It’s important to tell them what we know.” 

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Delirium linked to early death in advanced cancer patients

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A diagnosis of delirium during a visit to the emergency department (ED) is a poor prognostic factor for patients with advanced cancer, according to research published in The Oncologist.

The study showed that patients with advanced cancer who were diagnosed with delirium during an ED visit were more likely to be admitted to the hospital or intensive care unit (ICU) and more likely to die earlier than patients without delirium.

This shows the importance of accurately diagnosing delirium in advanced cancer patients, said Ahmed Elsayem, MD, of the University of Texas MD Anderson Cancer Center in Houston.

Previous studies have shown that delirium is associated with poor survival in advanced cancer patients being treated in ICUs or receiving palliative care in hospices, but no one had investigated whether the same was true for patients visiting EDs.

“To the best our knowledge, this is the first study to show the poor survival of advanced cancer patients in the emergency department setting,” Dr Elsayem said.

He and his colleagues previously conducted a study in which they assessed the frequency of delirium in advanced cancer patients visiting the ED at MD Anderson. The researchers tested for delirium using 2 questionnaires—the Confusion Assessment Method (CAM) and Memorial Delirium Assessment Scale (MDAS).

Questioning 243 patients in total, the team found that 44 patients, or 18%, were suffering with delirium according to at least 1 of the questionnaires.

In the current study, Dr Elsayem and his colleagues determined how many of these cancer patients, with and without delirium, were subsequently admitted to hospital and ICUs, as well as how long the patients lived after their visit to the ED.

Results

The rate of hospitalization was 82% among patients with delirium according to CAM and/or MDAS, 77% among patients with delirium according to MDAS only, and 49% among patients without delirium (P=0.0013). Rates of ICU admission were 18%, 14%, and 2%, respectively (P=0.0004).

The median overall survival was 1.23 months for patients with delirium according to CAM and/or MDAS, 4.70 months for patients with delirium according to MDAS only, and 10.45 months for patients without delirium. The difference between the patients with and without delirium was significant (P<0.0001).

Given the influence delirium appears to have on survival, Dr Elsayem said prompt diagnosis and management in hospital EDs is essential.

He noted that, in many cases, delirium in advanced cancer patients can be resolved by simply stopping or modifying their medication and treating any associated infections.

“Treating the triggers if known—such as stopping medications—is the main treatment for an episode of delirium,” Dr Elsayem said.

He also suggested that further research needs to be done on this topic, including conducting similar studies on delirium in advanced cancer patients in other EDs and with larger groups of patients.

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Photo courtesy of the CDC
Doctor evaluating patient

A diagnosis of delirium during a visit to the emergency department (ED) is a poor prognostic factor for patients with advanced cancer, according to research published in The Oncologist.

The study showed that patients with advanced cancer who were diagnosed with delirium during an ED visit were more likely to be admitted to the hospital or intensive care unit (ICU) and more likely to die earlier than patients without delirium.

This shows the importance of accurately diagnosing delirium in advanced cancer patients, said Ahmed Elsayem, MD, of the University of Texas MD Anderson Cancer Center in Houston.

Previous studies have shown that delirium is associated with poor survival in advanced cancer patients being treated in ICUs or receiving palliative care in hospices, but no one had investigated whether the same was true for patients visiting EDs.

“To the best our knowledge, this is the first study to show the poor survival of advanced cancer patients in the emergency department setting,” Dr Elsayem said.

He and his colleagues previously conducted a study in which they assessed the frequency of delirium in advanced cancer patients visiting the ED at MD Anderson. The researchers tested for delirium using 2 questionnaires—the Confusion Assessment Method (CAM) and Memorial Delirium Assessment Scale (MDAS).

Questioning 243 patients in total, the team found that 44 patients, or 18%, were suffering with delirium according to at least 1 of the questionnaires.

In the current study, Dr Elsayem and his colleagues determined how many of these cancer patients, with and without delirium, were subsequently admitted to hospital and ICUs, as well as how long the patients lived after their visit to the ED.

Results

The rate of hospitalization was 82% among patients with delirium according to CAM and/or MDAS, 77% among patients with delirium according to MDAS only, and 49% among patients without delirium (P=0.0013). Rates of ICU admission were 18%, 14%, and 2%, respectively (P=0.0004).

The median overall survival was 1.23 months for patients with delirium according to CAM and/or MDAS, 4.70 months for patients with delirium according to MDAS only, and 10.45 months for patients without delirium. The difference between the patients with and without delirium was significant (P<0.0001).

Given the influence delirium appears to have on survival, Dr Elsayem said prompt diagnosis and management in hospital EDs is essential.

He noted that, in many cases, delirium in advanced cancer patients can be resolved by simply stopping or modifying their medication and treating any associated infections.

“Treating the triggers if known—such as stopping medications—is the main treatment for an episode of delirium,” Dr Elsayem said.

He also suggested that further research needs to be done on this topic, including conducting similar studies on delirium in advanced cancer patients in other EDs and with larger groups of patients.

Photo courtesy of the CDC
Doctor evaluating patient

A diagnosis of delirium during a visit to the emergency department (ED) is a poor prognostic factor for patients with advanced cancer, according to research published in The Oncologist.

The study showed that patients with advanced cancer who were diagnosed with delirium during an ED visit were more likely to be admitted to the hospital or intensive care unit (ICU) and more likely to die earlier than patients without delirium.

This shows the importance of accurately diagnosing delirium in advanced cancer patients, said Ahmed Elsayem, MD, of the University of Texas MD Anderson Cancer Center in Houston.

Previous studies have shown that delirium is associated with poor survival in advanced cancer patients being treated in ICUs or receiving palliative care in hospices, but no one had investigated whether the same was true for patients visiting EDs.

“To the best our knowledge, this is the first study to show the poor survival of advanced cancer patients in the emergency department setting,” Dr Elsayem said.

He and his colleagues previously conducted a study in which they assessed the frequency of delirium in advanced cancer patients visiting the ED at MD Anderson. The researchers tested for delirium using 2 questionnaires—the Confusion Assessment Method (CAM) and Memorial Delirium Assessment Scale (MDAS).

Questioning 243 patients in total, the team found that 44 patients, or 18%, were suffering with delirium according to at least 1 of the questionnaires.

In the current study, Dr Elsayem and his colleagues determined how many of these cancer patients, with and without delirium, were subsequently admitted to hospital and ICUs, as well as how long the patients lived after their visit to the ED.

Results

The rate of hospitalization was 82% among patients with delirium according to CAM and/or MDAS, 77% among patients with delirium according to MDAS only, and 49% among patients without delirium (P=0.0013). Rates of ICU admission were 18%, 14%, and 2%, respectively (P=0.0004).

The median overall survival was 1.23 months for patients with delirium according to CAM and/or MDAS, 4.70 months for patients with delirium according to MDAS only, and 10.45 months for patients without delirium. The difference between the patients with and without delirium was significant (P<0.0001).

Given the influence delirium appears to have on survival, Dr Elsayem said prompt diagnosis and management in hospital EDs is essential.

He noted that, in many cases, delirium in advanced cancer patients can be resolved by simply stopping or modifying their medication and treating any associated infections.

“Treating the triggers if known—such as stopping medications—is the main treatment for an episode of delirium,” Dr Elsayem said.

He also suggested that further research needs to be done on this topic, including conducting similar studies on delirium in advanced cancer patients in other EDs and with larger groups of patients.

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Differential Response to Carfilzomib Based on Initial Therapy With Bortezomib in Multiple Myeloma

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Abstract 48: 2017 AVAHO Meeting

Background: Proteasome inhibitors (PIs) are efficacious in multiple myeloma (MM). In randomized phase 3 studies, carfilzomib doubled the progression free survival (PFS) compared to bortezomib from 9.4 mo to 18.7 mo (ENDEAVOR study) in relapsed and refractory MM. However, concern for suboptimal carfilzomib-based therapy (CBT) response in patients (pts) progressing on bortezomib-based therapy (BBT) suggests cross-resistance.

Methods: After IRB approval, all pts with symptomatic MM over the past 10 years at the Michael E. Debakey VA Medical Center with initial BBT followed by salvage CBT at progression were included. Primary aim was to evaluate ORR (PR + VGPR+CR) and PFS by IMWG criteria, in relapsed/refractory pts treated with salvage CBT based on initial BBT response (i.e., primary refractory + stable vs CR+PR+VGPR) or not.

Results: In this cohort, the median overall survival was 45 months. Pts initially treated with BBT had an ORR of 17/19 (89.4%) and median PFS of 7.7 mo. For 12 pts attaining PR, PFS was 4.3 mo. and for those achieving CR/VGPR, PFS was 9.1 mo. P = .03. Two pts were primary refractory to BBT and to CBT. For initial BBT responders, the ORR with CBT was 68.4% (13/19), median PFS was 5.26 mo 6/19 pts (32%) were CBT refractory. PFS during BBT for CBT responders vs CBT refractory pts was not statistically different. Among those who responded to both CBT and BBT, there was no significant correlation between the PFS (CR vs VGPR vs PR) with initial BBT and PFS with CBT.

Conclusions: In our retrospective analysis, pts who exhibited initial resistance to primary BBT did not benefit from salvage therapy with CBT, raising the possibility that hard-wired PI-resistance mechanisms exist. Among BBT responders, CBT ORR was 68%. However, the PFS with CBT
was significantly shorter than the published literature of CBT in RRMM naïve to PI leading us to hypothesize that uncharacterized resistance mechanisms from “priming” bortezomib leads to inferior outcome with salvage CBT. We conclude that CBT can be attempted in those who respond to BBT independent of depth of response or PFS duration. However, alternative therapies should be considered in pts with primary refractoriness to BBT.

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Abstract 48: 2017 AVAHO Meeting
Abstract 48: 2017 AVAHO Meeting

Background: Proteasome inhibitors (PIs) are efficacious in multiple myeloma (MM). In randomized phase 3 studies, carfilzomib doubled the progression free survival (PFS) compared to bortezomib from 9.4 mo to 18.7 mo (ENDEAVOR study) in relapsed and refractory MM. However, concern for suboptimal carfilzomib-based therapy (CBT) response in patients (pts) progressing on bortezomib-based therapy (BBT) suggests cross-resistance.

Methods: After IRB approval, all pts with symptomatic MM over the past 10 years at the Michael E. Debakey VA Medical Center with initial BBT followed by salvage CBT at progression were included. Primary aim was to evaluate ORR (PR + VGPR+CR) and PFS by IMWG criteria, in relapsed/refractory pts treated with salvage CBT based on initial BBT response (i.e., primary refractory + stable vs CR+PR+VGPR) or not.

Results: In this cohort, the median overall survival was 45 months. Pts initially treated with BBT had an ORR of 17/19 (89.4%) and median PFS of 7.7 mo. For 12 pts attaining PR, PFS was 4.3 mo. and for those achieving CR/VGPR, PFS was 9.1 mo. P = .03. Two pts were primary refractory to BBT and to CBT. For initial BBT responders, the ORR with CBT was 68.4% (13/19), median PFS was 5.26 mo 6/19 pts (32%) were CBT refractory. PFS during BBT for CBT responders vs CBT refractory pts was not statistically different. Among those who responded to both CBT and BBT, there was no significant correlation between the PFS (CR vs VGPR vs PR) with initial BBT and PFS with CBT.

Conclusions: In our retrospective analysis, pts who exhibited initial resistance to primary BBT did not benefit from salvage therapy with CBT, raising the possibility that hard-wired PI-resistance mechanisms exist. Among BBT responders, CBT ORR was 68%. However, the PFS with CBT
was significantly shorter than the published literature of CBT in RRMM naïve to PI leading us to hypothesize that uncharacterized resistance mechanisms from “priming” bortezomib leads to inferior outcome with salvage CBT. We conclude that CBT can be attempted in those who respond to BBT independent of depth of response or PFS duration. However, alternative therapies should be considered in pts with primary refractoriness to BBT.

Background: Proteasome inhibitors (PIs) are efficacious in multiple myeloma (MM). In randomized phase 3 studies, carfilzomib doubled the progression free survival (PFS) compared to bortezomib from 9.4 mo to 18.7 mo (ENDEAVOR study) in relapsed and refractory MM. However, concern for suboptimal carfilzomib-based therapy (CBT) response in patients (pts) progressing on bortezomib-based therapy (BBT) suggests cross-resistance.

Methods: After IRB approval, all pts with symptomatic MM over the past 10 years at the Michael E. Debakey VA Medical Center with initial BBT followed by salvage CBT at progression were included. Primary aim was to evaluate ORR (PR + VGPR+CR) and PFS by IMWG criteria, in relapsed/refractory pts treated with salvage CBT based on initial BBT response (i.e., primary refractory + stable vs CR+PR+VGPR) or not.

Results: In this cohort, the median overall survival was 45 months. Pts initially treated with BBT had an ORR of 17/19 (89.4%) and median PFS of 7.7 mo. For 12 pts attaining PR, PFS was 4.3 mo. and for those achieving CR/VGPR, PFS was 9.1 mo. P = .03. Two pts were primary refractory to BBT and to CBT. For initial BBT responders, the ORR with CBT was 68.4% (13/19), median PFS was 5.26 mo 6/19 pts (32%) were CBT refractory. PFS during BBT for CBT responders vs CBT refractory pts was not statistically different. Among those who responded to both CBT and BBT, there was no significant correlation between the PFS (CR vs VGPR vs PR) with initial BBT and PFS with CBT.

Conclusions: In our retrospective analysis, pts who exhibited initial resistance to primary BBT did not benefit from salvage therapy with CBT, raising the possibility that hard-wired PI-resistance mechanisms exist. Among BBT responders, CBT ORR was 68%. However, the PFS with CBT
was significantly shorter than the published literature of CBT in RRMM naïve to PI leading us to hypothesize that uncharacterized resistance mechanisms from “priming” bortezomib leads to inferior outcome with salvage CBT. We conclude that CBT can be attempted in those who respond to BBT independent of depth of response or PFS duration. However, alternative therapies should be considered in pts with primary refractoriness to BBT.

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ASCO updates guidelines on antiemetic use in cancer patients

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The American Society of Clinical Oncology (ASCO) has updated its clinical practice guidelines on the use of antiemetics in cancer patients.

The update, published in the Journal of Clinical Oncology, provides new evidence-based information on the appropriate use of olanzapine, NK1 receptor antagonists, and dexamethasone.

“The adverse impact of inadequately controlled nausea and vomiting on patients’ quality of life is well documented,” said Paul J. Hesketh, MD, co-chair of the ASCO expert panel that updated the guidelines.

“By following the ASCO antiemetics guideline, clinicians have the opportunity to improve patients’ quality of life by minimizing treatment-induced emesis.”

To update ASCO’s guidelines on antiemetics, the expert panel conducted a systematic review of the medical literature published between November 2009 and June 2016. The panel included members with expertise in medical oncology, radiation oncology, nursing, pharmacy, and health services research, as well as a patient representative.

“Tremendous progress has been realized over the last 25 years in the prevention of chemotherapy-induced nausea and vomiting with the introduction of new classes of antiemetic agents,” said Mark G. Kris, MD, co-chair of the expert panel that updated the guidelines.

“The full benefit of these treatment advances will only be realized, however, if evidence-based guidelines are fully implemented.”

Key recommendations in the updated guidelines include:

For adults receiving chemotherapy with a high risk for nausea and vomiting (eg, cisplatin or the combination of cyclophosphamide and an anthracycline), olanzapine should be added to standard antiemetic regimens (the combination of a 5-HT3 receptor antagonist, an NK1 receptor antagonist, and dexamethasone). Olanzapine also helps individuals who experience symptoms despite receiving medicines to prevent vomiting before chemotherapy is given.

For adults receiving carboplatin-based chemotherapy or high-dose chemotherapy and children receiving chemotherapy with a high risk for nausea and vomiting, an NK1 receptor antagonist should be added to the standard antiemetic regimen (the combination of 5-HT3 receptor antagonist and dexamethasone).

Dexamethasone treatment can be limited to the day of chemotherapy administration in patients receiving an anthracycline and cyclophosphamide.

Dronabinol and nabilone, cannabinoids approved by the US Food and Drug Administration, can be used to treat nausea and vomiting that is resistant to standard antiemetic therapies. Evidence remains insufficient to recommend medical marijuana for either prevention or treatment of nausea and vomiting in patients with cancer receiving chemotherapy or radiation therapy.

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Cancer patient receiving chemotherapy

The American Society of Clinical Oncology (ASCO) has updated its clinical practice guidelines on the use of antiemetics in cancer patients.

The update, published in the Journal of Clinical Oncology, provides new evidence-based information on the appropriate use of olanzapine, NK1 receptor antagonists, and dexamethasone.

“The adverse impact of inadequately controlled nausea and vomiting on patients’ quality of life is well documented,” said Paul J. Hesketh, MD, co-chair of the ASCO expert panel that updated the guidelines.

“By following the ASCO antiemetics guideline, clinicians have the opportunity to improve patients’ quality of life by minimizing treatment-induced emesis.”

To update ASCO’s guidelines on antiemetics, the expert panel conducted a systematic review of the medical literature published between November 2009 and June 2016. The panel included members with expertise in medical oncology, radiation oncology, nursing, pharmacy, and health services research, as well as a patient representative.

“Tremendous progress has been realized over the last 25 years in the prevention of chemotherapy-induced nausea and vomiting with the introduction of new classes of antiemetic agents,” said Mark G. Kris, MD, co-chair of the expert panel that updated the guidelines.

“The full benefit of these treatment advances will only be realized, however, if evidence-based guidelines are fully implemented.”

Key recommendations in the updated guidelines include:

For adults receiving chemotherapy with a high risk for nausea and vomiting (eg, cisplatin or the combination of cyclophosphamide and an anthracycline), olanzapine should be added to standard antiemetic regimens (the combination of a 5-HT3 receptor antagonist, an NK1 receptor antagonist, and dexamethasone). Olanzapine also helps individuals who experience symptoms despite receiving medicines to prevent vomiting before chemotherapy is given.

For adults receiving carboplatin-based chemotherapy or high-dose chemotherapy and children receiving chemotherapy with a high risk for nausea and vomiting, an NK1 receptor antagonist should be added to the standard antiemetic regimen (the combination of 5-HT3 receptor antagonist and dexamethasone).

Dexamethasone treatment can be limited to the day of chemotherapy administration in patients receiving an anthracycline and cyclophosphamide.

Dronabinol and nabilone, cannabinoids approved by the US Food and Drug Administration, can be used to treat nausea and vomiting that is resistant to standard antiemetic therapies. Evidence remains insufficient to recommend medical marijuana for either prevention or treatment of nausea and vomiting in patients with cancer receiving chemotherapy or radiation therapy.

Photo by Rhoda Baer
Cancer patient receiving chemotherapy

The American Society of Clinical Oncology (ASCO) has updated its clinical practice guidelines on the use of antiemetics in cancer patients.

The update, published in the Journal of Clinical Oncology, provides new evidence-based information on the appropriate use of olanzapine, NK1 receptor antagonists, and dexamethasone.

“The adverse impact of inadequately controlled nausea and vomiting on patients’ quality of life is well documented,” said Paul J. Hesketh, MD, co-chair of the ASCO expert panel that updated the guidelines.

“By following the ASCO antiemetics guideline, clinicians have the opportunity to improve patients’ quality of life by minimizing treatment-induced emesis.”

To update ASCO’s guidelines on antiemetics, the expert panel conducted a systematic review of the medical literature published between November 2009 and June 2016. The panel included members with expertise in medical oncology, radiation oncology, nursing, pharmacy, and health services research, as well as a patient representative.

“Tremendous progress has been realized over the last 25 years in the prevention of chemotherapy-induced nausea and vomiting with the introduction of new classes of antiemetic agents,” said Mark G. Kris, MD, co-chair of the expert panel that updated the guidelines.

“The full benefit of these treatment advances will only be realized, however, if evidence-based guidelines are fully implemented.”

Key recommendations in the updated guidelines include:

For adults receiving chemotherapy with a high risk for nausea and vomiting (eg, cisplatin or the combination of cyclophosphamide and an anthracycline), olanzapine should be added to standard antiemetic regimens (the combination of a 5-HT3 receptor antagonist, an NK1 receptor antagonist, and dexamethasone). Olanzapine also helps individuals who experience symptoms despite receiving medicines to prevent vomiting before chemotherapy is given.

For adults receiving carboplatin-based chemotherapy or high-dose chemotherapy and children receiving chemotherapy with a high risk for nausea and vomiting, an NK1 receptor antagonist should be added to the standard antiemetic regimen (the combination of 5-HT3 receptor antagonist and dexamethasone).

Dexamethasone treatment can be limited to the day of chemotherapy administration in patients receiving an anthracycline and cyclophosphamide.

Dronabinol and nabilone, cannabinoids approved by the US Food and Drug Administration, can be used to treat nausea and vomiting that is resistant to standard antiemetic therapies. Evidence remains insufficient to recommend medical marijuana for either prevention or treatment of nausea and vomiting in patients with cancer receiving chemotherapy or radiation therapy.

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Less lenalidomide may be more in frail elderly multiple myeloma patients

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In frail elderly patients with multiple myeloma, starting lenalidomide at low doses was associated with fewer adverse events and less treatment discontinuation, and did not compromise overall response rates, in a single-center, retrospective study conducted in Japan.

Although most of the 56 study patients received 5-10 mg/day of lenalidomide, not the recommended 25-mg/day dose, their overall response rate was 73% (complete response in 17% of patients, very good partial response in 19%, and partial response in 37%), Aya Nakaya, MD, PhD, of Kansai Medical University, Hirakata, and colleagues wrote (Acta Haematol. 2017;138:55-60). In addition, 23% of patients had stable disease and 4% had disease progression. Nine patients developed other types of malignancies during treatment with lenalidomide.

Starting patients on a reduced dose and increasing it gradually while monitoring carefully for adverse events meant that patients did not have to stop treatment, the researchers said. Continuous treatment may improve survival, and “treatment with lenalidomide for long periods of time, even in small doses, may yield favorable outcomes.”

The 30 men and 26 women, mean age 76.5 years, were consecutively diagnosed as transplant-ineligible patients with relapsed/refractory multiple myeloma; 34%, 32%, and 34% had stages I-III disease, respectively. The M-protein consisted of IgG in 52% of patients and IgA in 30%, with Bence-Jones protein detected in 14%.

They were treated with lenalidomide plus dexamethasone at a starting dose determined by the treating physician; 73% were treated with lenalidomide as a second-line regimen and 14% as a third-line regimen. During each 28-day treatment cycle, patients received lenalidomide on days 1-21 and dexamethasone (20 or 40 mg) on days 1, 8, 15, and 22.

The most common starting lenalidomide dose was 10 mg/day (45%), followed by 5 mg/day (21%), 15 mg/day (20%), 20 mg/day (4%), and 25 mg/day (10%). The treatment dose used for the longest period was 10 mg/day (46% of patients), followed by 5 mg/day (25%), 15 mg/day (16%), 20 mg/day (4%), and 25 mg/day (9%).

The most frequent reasons for dose reduction were renal dysfunction (54%), fatigue (20%), hematologic disorder (14%), and rash (9%).

The median treatment period was 9 months (range 1-60 months) and the median follow-up period was 16 months.

The median time to disease progression was 11.8 months (range 8.4-21.9), and the median overall survival was 39.2 months. For those who took 5-10 mg of lenalidomide, the median time to progression was 14.5 months; for those who took lenalidomide at a dose of more than 10 mg, the median time to progression was 8.9 months. The median overall survival of the patients who received a 5- to 10-mg dose of lenalidomide was 38.9 months; the median overall survival of the patients given a dose of more than 10 mg was not available.

The authors declared no competing financial interests in relation to this work.

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In frail elderly patients with multiple myeloma, starting lenalidomide at low doses was associated with fewer adverse events and less treatment discontinuation, and did not compromise overall response rates, in a single-center, retrospective study conducted in Japan.

Although most of the 56 study patients received 5-10 mg/day of lenalidomide, not the recommended 25-mg/day dose, their overall response rate was 73% (complete response in 17% of patients, very good partial response in 19%, and partial response in 37%), Aya Nakaya, MD, PhD, of Kansai Medical University, Hirakata, and colleagues wrote (Acta Haematol. 2017;138:55-60). In addition, 23% of patients had stable disease and 4% had disease progression. Nine patients developed other types of malignancies during treatment with lenalidomide.

Starting patients on a reduced dose and increasing it gradually while monitoring carefully for adverse events meant that patients did not have to stop treatment, the researchers said. Continuous treatment may improve survival, and “treatment with lenalidomide for long periods of time, even in small doses, may yield favorable outcomes.”

The 30 men and 26 women, mean age 76.5 years, were consecutively diagnosed as transplant-ineligible patients with relapsed/refractory multiple myeloma; 34%, 32%, and 34% had stages I-III disease, respectively. The M-protein consisted of IgG in 52% of patients and IgA in 30%, with Bence-Jones protein detected in 14%.

They were treated with lenalidomide plus dexamethasone at a starting dose determined by the treating physician; 73% were treated with lenalidomide as a second-line regimen and 14% as a third-line regimen. During each 28-day treatment cycle, patients received lenalidomide on days 1-21 and dexamethasone (20 or 40 mg) on days 1, 8, 15, and 22.

The most common starting lenalidomide dose was 10 mg/day (45%), followed by 5 mg/day (21%), 15 mg/day (20%), 20 mg/day (4%), and 25 mg/day (10%). The treatment dose used for the longest period was 10 mg/day (46% of patients), followed by 5 mg/day (25%), 15 mg/day (16%), 20 mg/day (4%), and 25 mg/day (9%).

The most frequent reasons for dose reduction were renal dysfunction (54%), fatigue (20%), hematologic disorder (14%), and rash (9%).

The median treatment period was 9 months (range 1-60 months) and the median follow-up period was 16 months.

The median time to disease progression was 11.8 months (range 8.4-21.9), and the median overall survival was 39.2 months. For those who took 5-10 mg of lenalidomide, the median time to progression was 14.5 months; for those who took lenalidomide at a dose of more than 10 mg, the median time to progression was 8.9 months. The median overall survival of the patients who received a 5- to 10-mg dose of lenalidomide was 38.9 months; the median overall survival of the patients given a dose of more than 10 mg was not available.

The authors declared no competing financial interests in relation to this work.

 

In frail elderly patients with multiple myeloma, starting lenalidomide at low doses was associated with fewer adverse events and less treatment discontinuation, and did not compromise overall response rates, in a single-center, retrospective study conducted in Japan.

Although most of the 56 study patients received 5-10 mg/day of lenalidomide, not the recommended 25-mg/day dose, their overall response rate was 73% (complete response in 17% of patients, very good partial response in 19%, and partial response in 37%), Aya Nakaya, MD, PhD, of Kansai Medical University, Hirakata, and colleagues wrote (Acta Haematol. 2017;138:55-60). In addition, 23% of patients had stable disease and 4% had disease progression. Nine patients developed other types of malignancies during treatment with lenalidomide.

Starting patients on a reduced dose and increasing it gradually while monitoring carefully for adverse events meant that patients did not have to stop treatment, the researchers said. Continuous treatment may improve survival, and “treatment with lenalidomide for long periods of time, even in small doses, may yield favorable outcomes.”

The 30 men and 26 women, mean age 76.5 years, were consecutively diagnosed as transplant-ineligible patients with relapsed/refractory multiple myeloma; 34%, 32%, and 34% had stages I-III disease, respectively. The M-protein consisted of IgG in 52% of patients and IgA in 30%, with Bence-Jones protein detected in 14%.

They were treated with lenalidomide plus dexamethasone at a starting dose determined by the treating physician; 73% were treated with lenalidomide as a second-line regimen and 14% as a third-line regimen. During each 28-day treatment cycle, patients received lenalidomide on days 1-21 and dexamethasone (20 or 40 mg) on days 1, 8, 15, and 22.

The most common starting lenalidomide dose was 10 mg/day (45%), followed by 5 mg/day (21%), 15 mg/day (20%), 20 mg/day (4%), and 25 mg/day (10%). The treatment dose used for the longest period was 10 mg/day (46% of patients), followed by 5 mg/day (25%), 15 mg/day (16%), 20 mg/day (4%), and 25 mg/day (9%).

The most frequent reasons for dose reduction were renal dysfunction (54%), fatigue (20%), hematologic disorder (14%), and rash (9%).

The median treatment period was 9 months (range 1-60 months) and the median follow-up period was 16 months.

The median time to disease progression was 11.8 months (range 8.4-21.9), and the median overall survival was 39.2 months. For those who took 5-10 mg of lenalidomide, the median time to progression was 14.5 months; for those who took lenalidomide at a dose of more than 10 mg, the median time to progression was 8.9 months. The median overall survival of the patients who received a 5- to 10-mg dose of lenalidomide was 38.9 months; the median overall survival of the patients given a dose of more than 10 mg was not available.

The authors declared no competing financial interests in relation to this work.

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Key clinical point: In frail elderly patients with multiple myeloma, starting lenalidomide at low doses was associated with fewer adverse events and less treatment discontinuation, and did not compromise overall response rates.

Major finding: Although most of the 56 study patients received 5-10 mg/day of lenalidomide, not the recommended 25-mg/day dose, their overall response rate was 73%.

Data source: A single-center, retrospective study of 56 consecutively diagnosed transplant-ineligible patients in Japan.

Disclosures: The authors declared no competing financial interests in relation to this work.

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GEP classifier predicts risk in MM

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A gene expression profiling (GEP) classifier can accurately identify high- and low-risk patients with multiple myeloma (MM), according to research published in Clinical Lymphoma, Myeloma and Leukemia.

The GEP classifier is known as SKY92, and researchers found they could accurately identify high-risk MM patients using SKY92 alone.

By combining SKY92 with the International Staging System (ISS), the team was able to identify low-risk MM patients as well.

“We have demonstrated the prognostic value of SKY92 not only as a marker of high risk, but also as a marker of low risk when combined with ISS,” said study author Erik H. van Beers, PhD, vice president of genomics at SkylineDx, the company that developed SKY92.

“Both validated markers may serve as the basis for the discovery of improved individualized therapies for patients with multiple myeloma.”

Dr van Beers and his colleagues compared 8 risk-assessment platforms to analyze gene expression data from 91 newly diagnosed MM patients. The patients were included in an independent dataset amassed by the Multiple Myeloma Research Foundation and the Multiple Myeloma Genomics Initiative (MMRF/MMGI).

The researchers used the GEP classifiers SKY92, UAMS70, UAMS80, IFM15, HM19, Cancer Testis Antigen, Centrosome Index, and Proliferation Index to identify high-risk patients.

Of the 8 classifiers, SKY92 identified the largest proportion (21%) of high-risk cases and also attained the highest Cox proportional hazard ratio (8.2) for overall survival (OS).

Additionally, SKY92 predicted 9 of the 13 (60%) deaths that occurred at 2 years and 16 of the 31 (52%) deaths at 5 years, a predictive rate that was higher than any of the other classifiers.

Dr van Beers and his colleagues also combined the SKY92 standard-risk classifier with the ISS to identify low-risk patients in the MMRF/MMGI cohort. This combination was recently identified as a marker for detecting low-risk MM.*

The SKY92/ISS marker identified 42% of patients as low risk, with their median OS not reached at 96 months. The low-risk classification was strongly supported by the achieved hazard ratio of 10.

“The MMRF/MMGI dataset was not part of our previous discovery*, which demonstrated that the combination of SKY92 and ISS identifies the lowest-risk patients with high accuracy and leaves the smallest proportion of patients identified as intermediate risk,” Dr van Beers said.  “Thus, the dataset remained available for independent validation—an important factor in the adoption of gene expression profiling tools.”

“We are pleased to have validated the SKY92/ISS low-risk marker by applying it to the well-characterized MMRF/MMGI cohort,” added study author Rafael Fonseca, MD, of the Mayo Clinic in Scottsdale, Arizona. “Our findings further strengthen the prognostic utility of the combination marker.”

*Kuiper R, van Duin M, van Vliet, MH, et al. Prediction of high- and low-risk multiple myeloma based on gene expression and the International Staging System. Blood. 2015;126(17):1996-2004.

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Micrograph showing MM

A gene expression profiling (GEP) classifier can accurately identify high- and low-risk patients with multiple myeloma (MM), according to research published in Clinical Lymphoma, Myeloma and Leukemia.

The GEP classifier is known as SKY92, and researchers found they could accurately identify high-risk MM patients using SKY92 alone.

By combining SKY92 with the International Staging System (ISS), the team was able to identify low-risk MM patients as well.

“We have demonstrated the prognostic value of SKY92 not only as a marker of high risk, but also as a marker of low risk when combined with ISS,” said study author Erik H. van Beers, PhD, vice president of genomics at SkylineDx, the company that developed SKY92.

“Both validated markers may serve as the basis for the discovery of improved individualized therapies for patients with multiple myeloma.”

Dr van Beers and his colleagues compared 8 risk-assessment platforms to analyze gene expression data from 91 newly diagnosed MM patients. The patients were included in an independent dataset amassed by the Multiple Myeloma Research Foundation and the Multiple Myeloma Genomics Initiative (MMRF/MMGI).

The researchers used the GEP classifiers SKY92, UAMS70, UAMS80, IFM15, HM19, Cancer Testis Antigen, Centrosome Index, and Proliferation Index to identify high-risk patients.

Of the 8 classifiers, SKY92 identified the largest proportion (21%) of high-risk cases and also attained the highest Cox proportional hazard ratio (8.2) for overall survival (OS).

Additionally, SKY92 predicted 9 of the 13 (60%) deaths that occurred at 2 years and 16 of the 31 (52%) deaths at 5 years, a predictive rate that was higher than any of the other classifiers.

Dr van Beers and his colleagues also combined the SKY92 standard-risk classifier with the ISS to identify low-risk patients in the MMRF/MMGI cohort. This combination was recently identified as a marker for detecting low-risk MM.*

The SKY92/ISS marker identified 42% of patients as low risk, with their median OS not reached at 96 months. The low-risk classification was strongly supported by the achieved hazard ratio of 10.

“The MMRF/MMGI dataset was not part of our previous discovery*, which demonstrated that the combination of SKY92 and ISS identifies the lowest-risk patients with high accuracy and leaves the smallest proportion of patients identified as intermediate risk,” Dr van Beers said.  “Thus, the dataset remained available for independent validation—an important factor in the adoption of gene expression profiling tools.”

“We are pleased to have validated the SKY92/ISS low-risk marker by applying it to the well-characterized MMRF/MMGI cohort,” added study author Rafael Fonseca, MD, of the Mayo Clinic in Scottsdale, Arizona. “Our findings further strengthen the prognostic utility of the combination marker.”

*Kuiper R, van Duin M, van Vliet, MH, et al. Prediction of high- and low-risk multiple myeloma based on gene expression and the International Staging System. Blood. 2015;126(17):1996-2004.

Micrograph showing MM

A gene expression profiling (GEP) classifier can accurately identify high- and low-risk patients with multiple myeloma (MM), according to research published in Clinical Lymphoma, Myeloma and Leukemia.

The GEP classifier is known as SKY92, and researchers found they could accurately identify high-risk MM patients using SKY92 alone.

By combining SKY92 with the International Staging System (ISS), the team was able to identify low-risk MM patients as well.

“We have demonstrated the prognostic value of SKY92 not only as a marker of high risk, but also as a marker of low risk when combined with ISS,” said study author Erik H. van Beers, PhD, vice president of genomics at SkylineDx, the company that developed SKY92.

“Both validated markers may serve as the basis for the discovery of improved individualized therapies for patients with multiple myeloma.”

Dr van Beers and his colleagues compared 8 risk-assessment platforms to analyze gene expression data from 91 newly diagnosed MM patients. The patients were included in an independent dataset amassed by the Multiple Myeloma Research Foundation and the Multiple Myeloma Genomics Initiative (MMRF/MMGI).

The researchers used the GEP classifiers SKY92, UAMS70, UAMS80, IFM15, HM19, Cancer Testis Antigen, Centrosome Index, and Proliferation Index to identify high-risk patients.

Of the 8 classifiers, SKY92 identified the largest proportion (21%) of high-risk cases and also attained the highest Cox proportional hazard ratio (8.2) for overall survival (OS).

Additionally, SKY92 predicted 9 of the 13 (60%) deaths that occurred at 2 years and 16 of the 31 (52%) deaths at 5 years, a predictive rate that was higher than any of the other classifiers.

Dr van Beers and his colleagues also combined the SKY92 standard-risk classifier with the ISS to identify low-risk patients in the MMRF/MMGI cohort. This combination was recently identified as a marker for detecting low-risk MM.*

The SKY92/ISS marker identified 42% of patients as low risk, with their median OS not reached at 96 months. The low-risk classification was strongly supported by the achieved hazard ratio of 10.

“The MMRF/MMGI dataset was not part of our previous discovery*, which demonstrated that the combination of SKY92 and ISS identifies the lowest-risk patients with high accuracy and leaves the smallest proportion of patients identified as intermediate risk,” Dr van Beers said.  “Thus, the dataset remained available for independent validation—an important factor in the adoption of gene expression profiling tools.”

“We are pleased to have validated the SKY92/ISS low-risk marker by applying it to the well-characterized MMRF/MMGI cohort,” added study author Rafael Fonseca, MD, of the Mayo Clinic in Scottsdale, Arizona. “Our findings further strengthen the prognostic utility of the combination marker.”

*Kuiper R, van Duin M, van Vliet, MH, et al. Prediction of high- and low-risk multiple myeloma based on gene expression and the International Staging System. Blood. 2015;126(17):1996-2004.

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