Multiple Myeloma

SAN DIEGO – Ixazomib improved progression-free survival following autologous stem cell transplantation (ASCT) in patients with newly diagnosed multiple myeloma, according to results of a double-blind, randomized, placebo-controlled, phase 3 trial.

Andrew Bowser/MDedge News

Treatment with the oral proteasome inhibitor for 24 months was well tolerated, had a low discontinuation rate, and improved progression-free survival by 39% versus placebo, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens.

These findings suggest ixazomib (Ninlaro) represents a “new treatment option for maintenance after transplantation,” Dr. Dimopoulos said at the annual meeting of the American Society of Hematology.

The trial, known as TOURMALINE-MM3, is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Dr. Dimopoulos. Lenalidomide is approved in that setting, but 29% of patients who start the treatment discontinue because of treatment-related adverse events.

“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said at an oral abstract session. Ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.

When asked by an attendee whether ixazomib would become “the standard of care” for younger patients with myeloma in this setting, Dr. Dimopoulos replied the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”

However, when pressed by an attendee to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.

“I think that instead of saying, ‘is ixazomib better than lenalidomide?’ or vice versa, it is better to see how one may combine those drugs in subsets of patients, or even combine these drugs with other agents,” he said.

The TOURMALINE-MM3 study included 656 patients randomized posttransplantation to receive weekly ixazomib or placebo for up to 2 years.

The median progression-free survival was 26.5 months for ixazomib versus 21.3 months for placebo (P = .002; hazard ratio, 0.720; 95% confidence interval, 0.582-0.890). Median overall survival had not been reached in either ixazomib or placebo arms as of this report, with a median follow-up of 31 months.

The discontinuation rate was 7% for ixazomib versus 5% for placebo, according to the investigator. Moreover, ixazomib was associated with “low toxicity” and no difference in the rates of new primary malignancies, at 3% in both arms.

A manuscript describing results of the TOURMALINE-MM3 study is in press in the Lancet, with an expected online publication date of Dec. 10, Dr. Dimopoulos told attendees. Other studies are ongoing to evaluate ixazomib combinations and treatment to progression in this setting.

TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib. Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceutical, Amgen, Bristol-Myers Squibb, and Celgene.

SOURCE: Dimopoulos MA et al. ASH 2018, Abstract 301.

SAN DIEGO – Ixazomib improved progression-free survival following autologous stem cell transplantation (ASCT) in patients with newly diagnosed multiple myeloma, according to results of a double-blind, randomized, placebo-controlled, phase 3 trial.

Andrew Bowser/MDedge News

Treatment with the oral proteasome inhibitor for 24 months was well tolerated, had a low discontinuation rate, and improved progression-free survival by 39% versus placebo, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens.

These findings suggest ixazomib (Ninlaro) represents a “new treatment option for maintenance after transplantation,” Dr. Dimopoulos said at the annual meeting of the American Society of Hematology.

The trial, known as TOURMALINE-MM3, is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Dr. Dimopoulos. Lenalidomide is approved in that setting, but 29% of patients who start the treatment discontinue because of treatment-related adverse events.

“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said at an oral abstract session. Ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.

When asked by an attendee whether ixazomib would become “the standard of care” for younger patients with myeloma in this setting, Dr. Dimopoulos replied the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”

However, when pressed by an attendee to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.

“I think that instead of saying, ‘is ixazomib better than lenalidomide?’ or vice versa, it is better to see how one may combine those drugs in subsets of patients, or even combine these drugs with other agents,” he said.

The TOURMALINE-MM3 study included 656 patients randomized posttransplantation to receive weekly ixazomib or placebo for up to 2 years.

The median progression-free survival was 26.5 months for ixazomib versus 21.3 months for placebo (P = .002; hazard ratio, 0.720; 95% confidence interval, 0.582-0.890). Median overall survival had not been reached in either ixazomib or placebo arms as of this report, with a median follow-up of 31 months.

The discontinuation rate was 7% for ixazomib versus 5% for placebo, according to the investigator. Moreover, ixazomib was associated with “low toxicity” and no difference in the rates of new primary malignancies, at 3% in both arms.

A manuscript describing results of the TOURMALINE-MM3 study is in press in the Lancet, with an expected online publication date of Dec. 10, Dr. Dimopoulos told attendees. Other studies are ongoing to evaluate ixazomib combinations and treatment to progression in this setting.

TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib. Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceutical, Amgen, Bristol-Myers Squibb, and Celgene.

SOURCE: Dimopoulos MA et al. ASH 2018, Abstract 301.

SAN DIEGO – Ixazomib improved progression-free survival following autologous stem cell transplantation (ASCT) in patients with newly diagnosed multiple myeloma, according to results of a double-blind, randomized, placebo-controlled, phase 3 trial.

Andrew Bowser/MDedge News

Treatment with the oral proteasome inhibitor for 24 months was well tolerated, had a low discontinuation rate, and improved progression-free survival by 39% versus placebo, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens.

These findings suggest ixazomib (Ninlaro) represents a “new treatment option for maintenance after transplantation,” Dr. Dimopoulos said at the annual meeting of the American Society of Hematology.

The trial, known as TOURMALINE-MM3, is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Dr. Dimopoulos. Lenalidomide is approved in that setting, but 29% of patients who start the treatment discontinue because of treatment-related adverse events.

“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said at an oral abstract session. Ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.

When asked by an attendee whether ixazomib would become “the standard of care” for younger patients with myeloma in this setting, Dr. Dimopoulos replied the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”

However, when pressed by an attendee to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.

“I think that instead of saying, ‘is ixazomib better than lenalidomide?’ or vice versa, it is better to see how one may combine those drugs in subsets of patients, or even combine these drugs with other agents,” he said.

The TOURMALINE-MM3 study included 656 patients randomized posttransplantation to receive weekly ixazomib or placebo for up to 2 years.

The median progression-free survival was 26.5 months for ixazomib versus 21.3 months for placebo (P = .002; hazard ratio, 0.720; 95% confidence interval, 0.582-0.890). Median overall survival had not been reached in either ixazomib or placebo arms as of this report, with a median follow-up of 31 months.

The discontinuation rate was 7% for ixazomib versus 5% for placebo, according to the investigator. Moreover, ixazomib was associated with “low toxicity” and no difference in the rates of new primary malignancies, at 3% in both arms.

A manuscript describing results of the TOURMALINE-MM3 study is in press in the Lancet, with an expected online publication date of Dec. 10, Dr. Dimopoulos told attendees. Other studies are ongoing to evaluate ixazomib combinations and treatment to progression in this setting.

TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib. Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceutical, Amgen, Bristol-Myers Squibb, and Celgene.

SOURCE: Dimopoulos MA et al. ASH 2018, Abstract 301.

Photo by Rhoda Baer

A retrospective study suggests one in seven patients with newly diagnosed multiple myeloma (MM) who are eligible for transplant may live at least as long as similar individuals in the general population.

The study included more than 7,000 MM patients, and 14.3% of those patients were able to meet or exceed their expected survival based on data from matched subjects in the general population.

Researchers believe that figure may be even higher today, as more than 90% of patients in this study were treated in the era before novel therapies became available.

Saad Z. Usmani, MD, of the Levine Cancer Institute/Atrium Health in Charlotte, North Carolina, and his colleagues described this study in Blood Cancer Journal.

The researchers studied 7,291 patients with newly diagnosed MM who were up to 75 years old and eligible for treatment with high-dose melphalan and autologous stem cell transplant. The patients were treated on clinical trials in 10 countries.

Factors associated with survival

Patients who had achieved a complete response (CR) 1 year after diagnosis had better median progression-free survival (PFS) than patients who did not achieve a CR—3.3 years and 2.6 years, respectively (P<0.0001).

Patients with a CR also had better median overall survival (OS)—8.5 years and 6.3 years, respectively (P<0.0001).

The identification of early CR as a predictor of PFS and OS “underscores the importance of depth of response as we explore novel regimens for newly diagnosed MM along with MRD [minimal residual disease] endpoints,” Dr. Usmani and his colleagues wrote.

They did acknowledge, however, that the patients studied were a selected group eligible for transplant and treated on trials.

Dr. Usmani and his colleagues also performed multivariate analyses to assess clinical variables at diagnosis associated with 10-year survival as compared with 2-year death. The results indicated that patients were less likely to be alive at 10 years if they:

• Were older than 65 (odds ratio [OR]for death, 1.87, P=0.002)
• Had an IgA isotype (OR=1.53; P=0.004)
• Had an albumin level lower than 3.5 g/dL (OR=1.36; P=0.023)
• Had a beta-2 microglobulin level of at least 3.5 mg/dL (OR=1.86; P<0.001)
• Had a serum creatinine level of at least 2 mg/dL (OR=1.77; P=0.005)
• Had a hemoglobin level below 10 g/dL (OR=1.55; P=0.003)
• Had a platelet count below 150,000/μL (OR=2.26; P<0.001).

Cytogenetic abnormalities did not independently predict long-term survival, but these abnormalities were obtained only by conventional band karyotyping and were not available for some patients.

Comparison to general population

Overall, the MM patients had a relative survival of about 0.9 compared with the matched general population. Relative survival was the ratio of observed survival among MM patients to expected survival in a population with comparable characteristics, such as nationality, age, and sex.

With follow-up out to about 20 years, the cure fraction—or the proportion of patients achieving or exceeding expected survival compared with the matched general population—was 14.3%.

The researchers noted that recent therapeutic advances “have re-ignited the debate on possible functional curability of a subset of MM patients. [T]here are perhaps more effective drugs and drug classes in the clinician’s armamentarium than [were] available for MM patients being treated in the 1990s or even early 2000s.”

“This may mean that the depth of response after induction therapy may continue to improve over time, potentially further improving the PFS/OS of [the] biologic subset who previously achieved [a partial response] yet had good long-term survival.”

Dr. Usmani reported relationships with AbbVie, Amgen, BMS, Celgene, Janssen, Takeda, Sanofi, SkylineDx, Array Biopharma, and Pharmacyclics.

Photo by Rhoda Baer

A retrospective study suggests one in seven patients with newly diagnosed multiple myeloma (MM) who are eligible for transplant may live at least as long as similar individuals in the general population.

The study included more than 7,000 MM patients, and 14.3% of those patients were able to meet or exceed their expected survival based on data from matched subjects in the general population.

Researchers believe that figure may be even higher today, as more than 90% of patients in this study were treated in the era before novel therapies became available.

Saad Z. Usmani, MD, of the Levine Cancer Institute/Atrium Health in Charlotte, North Carolina, and his colleagues described this study in Blood Cancer Journal.

The researchers studied 7,291 patients with newly diagnosed MM who were up to 75 years old and eligible for treatment with high-dose melphalan and autologous stem cell transplant. The patients were treated on clinical trials in 10 countries.

Factors associated with survival

Patients who had achieved a complete response (CR) 1 year after diagnosis had better median progression-free survival (PFS) than patients who did not achieve a CR—3.3 years and 2.6 years, respectively (P<0.0001).

Patients with a CR also had better median overall survival (OS)—8.5 years and 6.3 years, respectively (P<0.0001).

The identification of early CR as a predictor of PFS and OS “underscores the importance of depth of response as we explore novel regimens for newly diagnosed MM along with MRD [minimal residual disease] endpoints,” Dr. Usmani and his colleagues wrote.

They did acknowledge, however, that the patients studied were a selected group eligible for transplant and treated on trials.

Dr. Usmani and his colleagues also performed multivariate analyses to assess clinical variables at diagnosis associated with 10-year survival as compared with 2-year death. The results indicated that patients were less likely to be alive at 10 years if they:

• Were older than 65 (odds ratio [OR]for death, 1.87, P=0.002)
• Had an IgA isotype (OR=1.53; P=0.004)
• Had an albumin level lower than 3.5 g/dL (OR=1.36; P=0.023)
• Had a beta-2 microglobulin level of at least 3.5 mg/dL (OR=1.86; P<0.001)
• Had a serum creatinine level of at least 2 mg/dL (OR=1.77; P=0.005)
• Had a hemoglobin level below 10 g/dL (OR=1.55; P=0.003)
• Had a platelet count below 150,000/μL (OR=2.26; P<0.001).

Cytogenetic abnormalities did not independently predict long-term survival, but these abnormalities were obtained only by conventional band karyotyping and were not available for some patients.

Comparison to general population

Overall, the MM patients had a relative survival of about 0.9 compared with the matched general population. Relative survival was the ratio of observed survival among MM patients to expected survival in a population with comparable characteristics, such as nationality, age, and sex.

With follow-up out to about 20 years, the cure fraction—or the proportion of patients achieving or exceeding expected survival compared with the matched general population—was 14.3%.

The researchers noted that recent therapeutic advances “have re-ignited the debate on possible functional curability of a subset of MM patients. [T]here are perhaps more effective drugs and drug classes in the clinician’s armamentarium than [were] available for MM patients being treated in the 1990s or even early 2000s.”

“This may mean that the depth of response after induction therapy may continue to improve over time, potentially further improving the PFS/OS of [the] biologic subset who previously achieved [a partial response] yet had good long-term survival.”

Dr. Usmani reported relationships with AbbVie, Amgen, BMS, Celgene, Janssen, Takeda, Sanofi, SkylineDx, Array Biopharma, and Pharmacyclics.

Photo by Rhoda Baer

A retrospective study suggests one in seven patients with newly diagnosed multiple myeloma (MM) who are eligible for transplant may live at least as long as similar individuals in the general population.

The study included more than 7,000 MM patients, and 14.3% of those patients were able to meet or exceed their expected survival based on data from matched subjects in the general population.

Researchers believe that figure may be even higher today, as more than 90% of patients in this study were treated in the era before novel therapies became available.

Saad Z. Usmani, MD, of the Levine Cancer Institute/Atrium Health in Charlotte, North Carolina, and his colleagues described this study in Blood Cancer Journal.

The researchers studied 7,291 patients with newly diagnosed MM who were up to 75 years old and eligible for treatment with high-dose melphalan and autologous stem cell transplant. The patients were treated on clinical trials in 10 countries.

Factors associated with survival

Patients who had achieved a complete response (CR) 1 year after diagnosis had better median progression-free survival (PFS) than patients who did not achieve a CR—3.3 years and 2.6 years, respectively (P<0.0001).

Patients with a CR also had better median overall survival (OS)—8.5 years and 6.3 years, respectively (P<0.0001).

The identification of early CR as a predictor of PFS and OS “underscores the importance of depth of response as we explore novel regimens for newly diagnosed MM along with MRD [minimal residual disease] endpoints,” Dr. Usmani and his colleagues wrote.

They did acknowledge, however, that the patients studied were a selected group eligible for transplant and treated on trials.

Dr. Usmani and his colleagues also performed multivariate analyses to assess clinical variables at diagnosis associated with 10-year survival as compared with 2-year death. The results indicated that patients were less likely to be alive at 10 years if they:

• Were older than 65 (odds ratio [OR]for death, 1.87, P=0.002)
• Had an IgA isotype (OR=1.53; P=0.004)
• Had an albumin level lower than 3.5 g/dL (OR=1.36; P=0.023)
• Had a beta-2 microglobulin level of at least 3.5 mg/dL (OR=1.86; P<0.001)
• Had a serum creatinine level of at least 2 mg/dL (OR=1.77; P=0.005)
• Had a hemoglobin level below 10 g/dL (OR=1.55; P=0.003)
• Had a platelet count below 150,000/μL (OR=2.26; P<0.001).

Cytogenetic abnormalities did not independently predict long-term survival, but these abnormalities were obtained only by conventional band karyotyping and were not available for some patients.

Comparison to general population

Overall, the MM patients had a relative survival of about 0.9 compared with the matched general population. Relative survival was the ratio of observed survival among MM patients to expected survival in a population with comparable characteristics, such as nationality, age, and sex.

With follow-up out to about 20 years, the cure fraction—or the proportion of patients achieving or exceeding expected survival compared with the matched general population—was 14.3%.

The researchers noted that recent therapeutic advances “have re-ignited the debate on possible functional curability of a subset of MM patients. [T]here are perhaps more effective drugs and drug classes in the clinician’s armamentarium than [were] available for MM patients being treated in the 1990s or even early 2000s.”

“This may mean that the depth of response after induction therapy may continue to improve over time, potentially further improving the PFS/OS of [the] biologic subset who previously achieved [a partial response] yet had good long-term survival.”

Dr. Usmani reported relationships with AbbVie, Amgen, BMS, Celgene, Janssen, Takeda, Sanofi, SkylineDx, Array Biopharma, and Pharmacyclics.

Katja Weisel, MD

In Part 1 of this editorial, Katja Weisel, MD, of University Hospital Tubingen in Germany, describes the benefits of longer treatment in patients with multiple myeloma.

Despite recent progress in advancing the care of patients with multiple myeloma (MM), this cancer remains incurable.

Although novel combination regimens have driven major improvements in patient outcomes, most MM patients still experience multiple relapses, even those who respond to treatment initially.¹

Historically, MM was treated for a fixed duration, followed by a treatment-free interval and additional treatment at relapse. However, evidence suggests that continuous therapy after an initial response may be a better approach.^2,3

Pooled data from three large, phase 3 trials in newly diagnosed MM patients suggest that continuous therapy may lead to an increase in progression-free survival (PFS) and overall survival (OS).²

These results are supported by a meta-analysis, which showed favorable outcomes in PFS and OS with lenalidomide maintenance compared to placebo or observation in newly diagnosed MM patients who had received high-dose therapy and autologous stem cell transplant.³

Given these emerging findings and the availability of effective and tolerable therapies suitable for longer use, there is an opportunity to increase the adoption of this treatment strategy to improve outcomes for MM patients.

The concept of longer treatment for MM is not new. The first clinical trials in which researchers evaluated the efficacy and safety of this approach were conducted 40 years ago in patients initially treated with melphalan and prednisone. However, modest efficacy and substantial toxicity limited longer treatment with those agents.^4-7

The intervening years saw the introduction of new agents with different mechanisms of action, such as proteasome inhibitors and immunomodulators. These therapies, commonly used as initial treatment, provided physicians with additional options for treating patients longer.

Research has shown that longer treatment with immunomodulatory agents and proteasome inhibitors can be clinically effective.⁸

Longer treatment—integrated in the first-line treatment strategy and before a patient relapses—may enhance conventional induction strategies, resulting in better PFS and OS.^9,10

Continuous treatment, in which a patient receives treatment beyond a fixed induction period, has demonstrated extended PFS and OS as well.^2,3

Data supporting the benefits of prolonged therapy with immunomodulatory drugs has been a key driver behind the shifting paradigm in favor of longer treatment as the standard of care.^11,3

Additionally, continuing treatment with a proteasome inhibitor beyond induction therapy is associated with an improvement in the depth of response and prolonged OS.¹²

Longer treatment with proteasome inhibitors is also associated with deepening response rates and improved PFS following hematopoietic stem cell transplant.^13-15

Recent research has also shown that patients may achieve deeper remission with longer treatment,^16,17 overturning the long-held belief that longer duration of therapy can only extend a response rather than improve it.

Moreover, treating patients for longer may now be possible because of the favorable toxicity profile of some of the novel therapies currently available, which have fewer cumulative or late-onset toxicities.¹⁸ 

Dr. Weisel has received honoraria and/or consultancy fees from Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda. She has received research funding from Amgen, Celgene, Sanofi, and Janssen.

 The W2O Group provided writing support for this editorial, which was funded by Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

1.   Lonial S. Hematology Am Soc Hematol Educ Program. 2010; 2010:303-9. doi: 10.1182/asheducation-2010.1.303

2.   Palumbo A et al. J Clin Oncol. 2015; 33(30):3459-66. doi: 10.1200/JCO.2014.60.2466

3.   McCarthy PL et al. J Clin Oncol. 2017; 35(29):3279-3289. doi: 10.1200/JCO.2017.72.6679

4.  Joks M et al. Eur J Haematol. 2015 ;94(2):109-14. doi: 10.1111/ejh.12412

5.   Berenson JR et al. Blood. 2002; 99:3163-8. doi: http://www.bloodjournal.org/content/99/9/3163.long

6.   Shustik C et al. Br J Haematol. 2007; 126:201-11. doi: https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2141.2006.06405.x

7.   Fritz E, Ludwig H. Ann Oncol. 2000 Nov;11(11):1427-36

8.   Ludwig H et al. Blood. 2012; 119:3003-3015. doi: https://doi.org/10.1182/blood-2011-11-374249

9.   Mateos MV et al. Am J Hematol. 2015; 90(4):314-9. doi: 10.1002/ajh.23933

10. Benboubker L et al. N Engl J Med. 2014; 371(10):906-17. doi: 10.1056/NEJMoa1402551

11. Holstein SA et al. Lancet Haematol. 2017; 4(9):e431-e442. doi: 10.1016/S2352-3026(17)30140-0

12. Mateos MV et al. Blood. 2014; 124:1887-1893. doi: https://doi.org/10.1182/blood-2014-05-573733

13. Sonneveld P et al. ASH Annual Meeting Abstracts. Blood. 2010;116. Abstract 40

14. Rosiñol L et al. Blood. 2012; 120(8):1589-96. doi: https://doi.org/10.1182/blood-2012-02-408922

15. Richardson PG et al. N Engl J Med. 2005; 352(24):2487-98. doi: 10.1056/NEJMoa043445

16. de Tute RM et al. ASH Annual Meeting Abstracts. Blood. 2017; 130: 904. Abstract 904

17. Dimopoulos M et al. J Hematol Oncol. 2018;11(1):49. doi: 10.1186/s13045-018-0583-7

18. Lipe B et al. Blood Cancer J. 2016; 6(10): e485. doi: 10.1038/bcj.2016.89

Katja Weisel, MD

In Part 1 of this editorial, Katja Weisel, MD, of University Hospital Tubingen in Germany, describes the benefits of longer treatment in patients with multiple myeloma.

Despite recent progress in advancing the care of patients with multiple myeloma (MM), this cancer remains incurable.

Although novel combination regimens have driven major improvements in patient outcomes, most MM patients still experience multiple relapses, even those who respond to treatment initially.¹

Historically, MM was treated for a fixed duration, followed by a treatment-free interval and additional treatment at relapse. However, evidence suggests that continuous therapy after an initial response may be a better approach.^2,3

Pooled data from three large, phase 3 trials in newly diagnosed MM patients suggest that continuous therapy may lead to an increase in progression-free survival (PFS) and overall survival (OS).²

These results are supported by a meta-analysis, which showed favorable outcomes in PFS and OS with lenalidomide maintenance compared to placebo or observation in newly diagnosed MM patients who had received high-dose therapy and autologous stem cell transplant.³

Given these emerging findings and the availability of effective and tolerable therapies suitable for longer use, there is an opportunity to increase the adoption of this treatment strategy to improve outcomes for MM patients.

The concept of longer treatment for MM is not new. The first clinical trials in which researchers evaluated the efficacy and safety of this approach were conducted 40 years ago in patients initially treated with melphalan and prednisone. However, modest efficacy and substantial toxicity limited longer treatment with those agents.^4-7

The intervening years saw the introduction of new agents with different mechanisms of action, such as proteasome inhibitors and immunomodulators. These therapies, commonly used as initial treatment, provided physicians with additional options for treating patients longer.

Research has shown that longer treatment with immunomodulatory agents and proteasome inhibitors can be clinically effective.⁸

Longer treatment—integrated in the first-line treatment strategy and before a patient relapses—may enhance conventional induction strategies, resulting in better PFS and OS.^9,10

Continuous treatment, in which a patient receives treatment beyond a fixed induction period, has demonstrated extended PFS and OS as well.^2,3

Data supporting the benefits of prolonged therapy with immunomodulatory drugs has been a key driver behind the shifting paradigm in favor of longer treatment as the standard of care.^11,3

Additionally, continuing treatment with a proteasome inhibitor beyond induction therapy is associated with an improvement in the depth of response and prolonged OS.¹²

Longer treatment with proteasome inhibitors is also associated with deepening response rates and improved PFS following hematopoietic stem cell transplant.^13-15

Recent research has also shown that patients may achieve deeper remission with longer treatment,^16,17 overturning the long-held belief that longer duration of therapy can only extend a response rather than improve it.

Moreover, treating patients for longer may now be possible because of the favorable toxicity profile of some of the novel therapies currently available, which have fewer cumulative or late-onset toxicities.¹⁸ 

Dr. Weisel has received honoraria and/or consultancy fees from Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda. She has received research funding from Amgen, Celgene, Sanofi, and Janssen.

 The W2O Group provided writing support for this editorial, which was funded by Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

1.   Lonial S. Hematology Am Soc Hematol Educ Program. 2010; 2010:303-9. doi: 10.1182/asheducation-2010.1.303

2.   Palumbo A et al. J Clin Oncol. 2015; 33(30):3459-66. doi: 10.1200/JCO.2014.60.2466

3.   McCarthy PL et al. J Clin Oncol. 2017; 35(29):3279-3289. doi: 10.1200/JCO.2017.72.6679

4.  Joks M et al. Eur J Haematol. 2015 ;94(2):109-14. doi: 10.1111/ejh.12412

5.   Berenson JR et al. Blood. 2002; 99:3163-8. doi: http://www.bloodjournal.org/content/99/9/3163.long

6.   Shustik C et al. Br J Haematol. 2007; 126:201-11. doi: https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2141.2006.06405.x

7.   Fritz E, Ludwig H. Ann Oncol. 2000 Nov;11(11):1427-36

8.   Ludwig H et al. Blood. 2012; 119:3003-3015. doi: https://doi.org/10.1182/blood-2011-11-374249

9.   Mateos MV et al. Am J Hematol. 2015; 90(4):314-9. doi: 10.1002/ajh.23933

10. Benboubker L et al. N Engl J Med. 2014; 371(10):906-17. doi: 10.1056/NEJMoa1402551

11. Holstein SA et al. Lancet Haematol. 2017; 4(9):e431-e442. doi: 10.1016/S2352-3026(17)30140-0

12. Mateos MV et al. Blood. 2014; 124:1887-1893. doi: https://doi.org/10.1182/blood-2014-05-573733

13. Sonneveld P et al. ASH Annual Meeting Abstracts. Blood. 2010;116. Abstract 40

14. Rosiñol L et al. Blood. 2012; 120(8):1589-96. doi: https://doi.org/10.1182/blood-2012-02-408922

15. Richardson PG et al. N Engl J Med. 2005; 352(24):2487-98. doi: 10.1056/NEJMoa043445

16. de Tute RM et al. ASH Annual Meeting Abstracts. Blood. 2017; 130: 904. Abstract 904

17. Dimopoulos M et al. J Hematol Oncol. 2018;11(1):49. doi: 10.1186/s13045-018-0583-7

18. Lipe B et al. Blood Cancer J. 2016; 6(10): e485. doi: 10.1038/bcj.2016.89

Katja Weisel, MD

In Part 1 of this editorial, Katja Weisel, MD, of University Hospital Tubingen in Germany, describes the benefits of longer treatment in patients with multiple myeloma.

Despite recent progress in advancing the care of patients with multiple myeloma (MM), this cancer remains incurable.

Although novel combination regimens have driven major improvements in patient outcomes, most MM patients still experience multiple relapses, even those who respond to treatment initially.¹

Historically, MM was treated for a fixed duration, followed by a treatment-free interval and additional treatment at relapse. However, evidence suggests that continuous therapy after an initial response may be a better approach.^2,3

Pooled data from three large, phase 3 trials in newly diagnosed MM patients suggest that continuous therapy may lead to an increase in progression-free survival (PFS) and overall survival (OS).²

These results are supported by a meta-analysis, which showed favorable outcomes in PFS and OS with lenalidomide maintenance compared to placebo or observation in newly diagnosed MM patients who had received high-dose therapy and autologous stem cell transplant.³

Given these emerging findings and the availability of effective and tolerable therapies suitable for longer use, there is an opportunity to increase the adoption of this treatment strategy to improve outcomes for MM patients.

The concept of longer treatment for MM is not new. The first clinical trials in which researchers evaluated the efficacy and safety of this approach were conducted 40 years ago in patients initially treated with melphalan and prednisone. However, modest efficacy and substantial toxicity limited longer treatment with those agents.^4-7

The intervening years saw the introduction of new agents with different mechanisms of action, such as proteasome inhibitors and immunomodulators. These therapies, commonly used as initial treatment, provided physicians with additional options for treating patients longer.

Research has shown that longer treatment with immunomodulatory agents and proteasome inhibitors can be clinically effective.⁸

Longer treatment—integrated in the first-line treatment strategy and before a patient relapses—may enhance conventional induction strategies, resulting in better PFS and OS.^9,10

Continuous treatment, in which a patient receives treatment beyond a fixed induction period, has demonstrated extended PFS and OS as well.^2,3

Data supporting the benefits of prolonged therapy with immunomodulatory drugs has been a key driver behind the shifting paradigm in favor of longer treatment as the standard of care.^11,3

Additionally, continuing treatment with a proteasome inhibitor beyond induction therapy is associated with an improvement in the depth of response and prolonged OS.¹²

Longer treatment with proteasome inhibitors is also associated with deepening response rates and improved PFS following hematopoietic stem cell transplant.^13-15

Recent research has also shown that patients may achieve deeper remission with longer treatment,^16,17 overturning the long-held belief that longer duration of therapy can only extend a response rather than improve it.

Moreover, treating patients for longer may now be possible because of the favorable toxicity profile of some of the novel therapies currently available, which have fewer cumulative or late-onset toxicities.¹⁸ 

Dr. Weisel has received honoraria and/or consultancy fees from Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda. She has received research funding from Amgen, Celgene, Sanofi, and Janssen.

 The W2O Group provided writing support for this editorial, which was funded by Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

1.   Lonial S. Hematology Am Soc Hematol Educ Program. 2010; 2010:303-9. doi: 10.1182/asheducation-2010.1.303

2.   Palumbo A et al. J Clin Oncol. 2015; 33(30):3459-66. doi: 10.1200/JCO.2014.60.2466

3.   McCarthy PL et al. J Clin Oncol. 2017; 35(29):3279-3289. doi: 10.1200/JCO.2017.72.6679

4.  Joks M et al. Eur J Haematol. 2015 ;94(2):109-14. doi: 10.1111/ejh.12412

5.   Berenson JR et al. Blood. 2002; 99:3163-8. doi: http://www.bloodjournal.org/content/99/9/3163.long

6.   Shustik C et al. Br J Haematol. 2007; 126:201-11. doi: https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2141.2006.06405.x

7.   Fritz E, Ludwig H. Ann Oncol. 2000 Nov;11(11):1427-36

8.   Ludwig H et al. Blood. 2012; 119:3003-3015. doi: https://doi.org/10.1182/blood-2011-11-374249

9.   Mateos MV et al. Am J Hematol. 2015; 90(4):314-9. doi: 10.1002/ajh.23933

10. Benboubker L et al. N Engl J Med. 2014; 371(10):906-17. doi: 10.1056/NEJMoa1402551

11. Holstein SA et al. Lancet Haematol. 2017; 4(9):e431-e442. doi: 10.1016/S2352-3026(17)30140-0

12. Mateos MV et al. Blood. 2014; 124:1887-1893. doi: https://doi.org/10.1182/blood-2014-05-573733

13. Sonneveld P et al. ASH Annual Meeting Abstracts. Blood. 2010;116. Abstract 40

14. Rosiñol L et al. Blood. 2012; 120(8):1589-96. doi: https://doi.org/10.1182/blood-2012-02-408922

15. Richardson PG et al. N Engl J Med. 2005; 352(24):2487-98. doi: 10.1056/NEJMoa043445

16. de Tute RM et al. ASH Annual Meeting Abstracts. Blood. 2017; 130: 904. Abstract 904

17. Dimopoulos M et al. J Hematol Oncol. 2018;11(1):49. doi: 10.1186/s13045-018-0583-7

18. Lipe B et al. Blood Cancer J. 2016; 6(10): e485. doi: 10.1038/bcj.2016.89

Micrograph showing MM

In Part 2 of this editorial, Katja Weisel, MD, of University Hospital Tubingen in Germany, addresses the barriers to longer treatment in patients with multiple myeloma.

Attitudes regarding longer treatment can present barriers to widespread adoption of this approach in multiple myeloma (MM).

Indeed, some clinicians continue to follow a fixed-duration approach to treatment in MM, only considering further treatment once the patient has relapsed rather than treating the patient until disease progression.

In the MM community, some are reluctant to adopt a strategy of treating longer because of the modest efficacy gains observed with early research or concern over tolerability issues, including the risk of developing peripheral neuropathy or secondary malignancies.¹

Others are uncertain about the optimal duration of therapy or the selection of an agent that will balance any potential gain in depth of response with the risk of late-onset or cumulative toxicities.

The potentially high cost of longer treatment for patients, their families, and/or the healthcare system overall also presents a challenge.

It is feasible that treating patients for longer may drive up healthcare utilization and take a toll on patients and caregivers, who may incur out-of-pocket costs because of the need to travel to a hospital or doctor’s office for intravenous therapies, requiring them to miss work.²

It is important to recognize, however, that more convenient all-oral treatment regimens are now available that do not require infusion at a hospital or clinic. Furthermore, results from recent studies suggest the majority of cancer patients prefer oral over intravenous therapies, which could reduce non-pharmacy healthcare costs.^3,4

Healthcare providers might be more likely to accept and adopt a longer treatment approach for MM if they had access to data describing the optimal duration, dosage, schedule, toxicity, and quality of life standards.

Ongoing, randomized, phase 3 trials are evaluating the benefits of treating longer with an oral proteasome inhibitor in patients with newly diagnosed MM.^5,6

Updated treatment guidelines and consensus statements will provide further guidance for clinicians on the benefits of maintenance therapy in both transplant-eligible and -ineligible patients with newly diagnosed MM.

The recently updated MM guidelines from the European Society for Medical Oncology (ESMO) recommend longer treatment or maintenance therapy in patients who have undergone hematopoietic stem cell transplant (HSCT).⁷

Based on evidence from studies such as FIRST and SWOG S0777, ESMO also recommends continuous treatment or treatment until progression with lenalidomide-dexamethasone and bortezomib-lenalidomide-dexamethasone in MM patients who are ineligible for HSCT.^7-9

As there is no one-size-fits-all treatment approach in MM, a personalized treatment plan should be designed for each patient. This plan should take into account a number of factors, including age, disease characteristics, performance status, treatment history, and the patient’s goals of care and personal preferences.¹⁰

If the patient is a candidate for longer treatment, the clinician should carefully weigh the potential impact on disease-free and overall survival against the potential side effects, as well as assess the patient’s likelihood of adhering to the medication.

With the availability of newer, less-toxic medications that can be tolerated for a greater duration and are easy to administer, aiding in overall treatment compliance, sustained remissions are possible.^11-13

Forty years ago, MM patients had very few treatment options, and the 5-year survival rate was 26%.¹⁴

Since then, novel therapies, including proteasome inhibitors and immunomodulatory drugs, have replaced conventional cytotoxic chemotherapy, leading to major improvements in survival.^15,16

With emerging research that supports the value of longer treatment strategies for both patients and the healthcare system, clinicians will have a proven strategy to help their patients attain long-term disease control while maintaining quality of life.^{2, 17-19} 

Dr. Weisel has received honoraria and/or consultancy fees from Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda. She has received research funding from Amgen, Celgene, Sanofi, and Janssen.

 The W2O Group provided writing support for this editorial, which was funded by Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

1.  Lipe B et al. Blood Cancer J. 2016; 6(10): e485. doi:  10.1038/bcj.2016.89

2.   Goodwin J et al. Cancer Nurs. 2013; 36(4):301-8. doi: 10.1097/NCC.0b013e3182693522

3.   Eek D et al. Patient Prefer Adherence. 2016; 10:1609-21. doi: 10.2147/PPA.S106629

4.   Bauer S et al. Value in Health. 2017; 20: A451. Abstract PCN217. doi: https://doi.org/10.1016/j.jval.2017.08.299

5.   A Study of Oral Ixazomib Citrate (MLN9708) Maintenance Therapy in Participants With Multiple Myeloma Following Autologous Stem Cell Transplant. (2014). Retrieved from https://clinicaltrials.gov/ct2/show/NCT02181413 (Identification No. NCT02181413).

6.   A Study of Oral Ixazomib Maintenance Therapy in Patients With Newly Diagnosed Multiple Myeloma Not Treated With Stem Cell Transplantation. (2014). Retrieved from https://clinicaltrials.gov/ct2/show/NCT02312258 (Identification No. NCT02312258).

7. Moreau P et al. Ann Oncol. 2017; 28: iv52-iv61. doi: https://org/10.1093/annonc/mdx096

8.   Facon T et al. Blood. 2018131(3):301-310. doi: 10.1182/blood-2017-07-795047

9.   Durie BG et al. Lancet. 2017; 389(10068):519-527. doi: 10.1016/S0140-6736(16)31594-X.

10.  Laubach J et al. Leukemia. 2016; 30(5):1005-17. doi: 10.1038/leu.2015.356

11.  Ludwig H et al. Blood. 2012; 119: 3003-3015. doi: https://doi.org/10.1182/blood-2011-11-374249

12.  Lehners N et al. Cancer Med. 2018; 7(2): 307–316. doi: 10.1002/cam4.1283

13.  Attal M et al. N Engl J Med. 2012; 366:1872-1791. doi: 10.1056/NEJMoa1114138

14.  National Cancer Institute. SEER Cancer Statistics Review (CSR) 1975-2014. National Cancer Institute. https://seer.cancer.gov/csr/1975_2014/. Accessed March 28, 2018.

15.  Kumar SK et al. Blood. 2008 Mar 1;111(5):2516-20. doi: 10.1182/blood-2007-10-116129

16.  Fonseca R et al. Leukemia. 2017 Sep;31(9):1915-1921. doi: 10.1038/leu.2016.380

17.  Palumbo A, Niesvizky R. Leuk Res. 2012; 36 Suppl 1:S19-26. doi: 10.1016/S0145-2126(12)70005-X

18.  Girnius S, Munshi NC. Leuk Suppl. 2013; 2(Suppl 1): S3–S9. doi:  10.1038/leusup.2013.2

19.  Mateos M-V, San Miguel JF. Hematology Am Soc Hematol Educ Program. 2013; 2013:488-95. doi: 10.1182/asheducation-2013.1.488

Micrograph showing MM

In Part 2 of this editorial, Katja Weisel, MD, of University Hospital Tubingen in Germany, addresses the barriers to longer treatment in patients with multiple myeloma.

Attitudes regarding longer treatment can present barriers to widespread adoption of this approach in multiple myeloma (MM).

Indeed, some clinicians continue to follow a fixed-duration approach to treatment in MM, only considering further treatment once the patient has relapsed rather than treating the patient until disease progression.

In the MM community, some are reluctant to adopt a strategy of treating longer because of the modest efficacy gains observed with early research or concern over tolerability issues, including the risk of developing peripheral neuropathy or secondary malignancies.¹

Others are uncertain about the optimal duration of therapy or the selection of an agent that will balance any potential gain in depth of response with the risk of late-onset or cumulative toxicities.

The potentially high cost of longer treatment for patients, their families, and/or the healthcare system overall also presents a challenge.

It is feasible that treating patients for longer may drive up healthcare utilization and take a toll on patients and caregivers, who may incur out-of-pocket costs because of the need to travel to a hospital or doctor’s office for intravenous therapies, requiring them to miss work.²

It is important to recognize, however, that more convenient all-oral treatment regimens are now available that do not require infusion at a hospital or clinic. Furthermore, results from recent studies suggest the majority of cancer patients prefer oral over intravenous therapies, which could reduce non-pharmacy healthcare costs.^3,4

Healthcare providers might be more likely to accept and adopt a longer treatment approach for MM if they had access to data describing the optimal duration, dosage, schedule, toxicity, and quality of life standards.

Ongoing, randomized, phase 3 trials are evaluating the benefits of treating longer with an oral proteasome inhibitor in patients with newly diagnosed MM.^5,6

Updated treatment guidelines and consensus statements will provide further guidance for clinicians on the benefits of maintenance therapy in both transplant-eligible and -ineligible patients with newly diagnosed MM.

The recently updated MM guidelines from the European Society for Medical Oncology (ESMO) recommend longer treatment or maintenance therapy in patients who have undergone hematopoietic stem cell transplant (HSCT).⁷

Based on evidence from studies such as FIRST and SWOG S0777, ESMO also recommends continuous treatment or treatment until progression with lenalidomide-dexamethasone and bortezomib-lenalidomide-dexamethasone in MM patients who are ineligible for HSCT.^7-9

As there is no one-size-fits-all treatment approach in MM, a personalized treatment plan should be designed for each patient. This plan should take into account a number of factors, including age, disease characteristics, performance status, treatment history, and the patient’s goals of care and personal preferences.¹⁰

If the patient is a candidate for longer treatment, the clinician should carefully weigh the potential impact on disease-free and overall survival against the potential side effects, as well as assess the patient’s likelihood of adhering to the medication.

With the availability of newer, less-toxic medications that can be tolerated for a greater duration and are easy to administer, aiding in overall treatment compliance, sustained remissions are possible.^11-13

Forty years ago, MM patients had very few treatment options, and the 5-year survival rate was 26%.¹⁴

Since then, novel therapies, including proteasome inhibitors and immunomodulatory drugs, have replaced conventional cytotoxic chemotherapy, leading to major improvements in survival.^15,16

With emerging research that supports the value of longer treatment strategies for both patients and the healthcare system, clinicians will have a proven strategy to help their patients attain long-term disease control while maintaining quality of life.^{2, 17-19} 

Dr. Weisel has received honoraria and/or consultancy fees from Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda. She has received research funding from Amgen, Celgene, Sanofi, and Janssen.

 The W2O Group provided writing support for this editorial, which was funded by Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

1.  Lipe B et al. Blood Cancer J. 2016; 6(10): e485. doi:  10.1038/bcj.2016.89

2.   Goodwin J et al. Cancer Nurs. 2013; 36(4):301-8. doi: 10.1097/NCC.0b013e3182693522

3.   Eek D et al. Patient Prefer Adherence. 2016; 10:1609-21. doi: 10.2147/PPA.S106629

4.   Bauer S et al. Value in Health. 2017; 20: A451. Abstract PCN217. doi: https://doi.org/10.1016/j.jval.2017.08.299

5.   A Study of Oral Ixazomib Citrate (MLN9708) Maintenance Therapy in Participants With Multiple Myeloma Following Autologous Stem Cell Transplant. (2014). Retrieved from https://clinicaltrials.gov/ct2/show/NCT02181413 (Identification No. NCT02181413).

6.   A Study of Oral Ixazomib Maintenance Therapy in Patients With Newly Diagnosed Multiple Myeloma Not Treated With Stem Cell Transplantation. (2014). Retrieved from https://clinicaltrials.gov/ct2/show/NCT02312258 (Identification No. NCT02312258).

7. Moreau P et al. Ann Oncol. 2017; 28: iv52-iv61. doi: https://org/10.1093/annonc/mdx096

8.   Facon T et al. Blood. 2018131(3):301-310. doi: 10.1182/blood-2017-07-795047

9.   Durie BG et al. Lancet. 2017; 389(10068):519-527. doi: 10.1016/S0140-6736(16)31594-X.

10.  Laubach J et al. Leukemia. 2016; 30(5):1005-17. doi: 10.1038/leu.2015.356

11.  Ludwig H et al. Blood. 2012; 119: 3003-3015. doi: https://doi.org/10.1182/blood-2011-11-374249

12.  Lehners N et al. Cancer Med. 2018; 7(2): 307–316. doi: 10.1002/cam4.1283

13.  Attal M et al. N Engl J Med. 2012; 366:1872-1791. doi: 10.1056/NEJMoa1114138

14.  National Cancer Institute. SEER Cancer Statistics Review (CSR) 1975-2014. National Cancer Institute. https://seer.cancer.gov/csr/1975_2014/. Accessed March 28, 2018.

15.  Kumar SK et al. Blood. 2008 Mar 1;111(5):2516-20. doi: 10.1182/blood-2007-10-116129

16.  Fonseca R et al. Leukemia. 2017 Sep;31(9):1915-1921. doi: 10.1038/leu.2016.380

17.  Palumbo A, Niesvizky R. Leuk Res. 2012; 36 Suppl 1:S19-26. doi: 10.1016/S0145-2126(12)70005-X

18.  Girnius S, Munshi NC. Leuk Suppl. 2013; 2(Suppl 1): S3–S9. doi:  10.1038/leusup.2013.2

19.  Mateos M-V, San Miguel JF. Hematology Am Soc Hematol Educ Program. 2013; 2013:488-95. doi: 10.1182/asheducation-2013.1.488

Micrograph showing MM

In Part 2 of this editorial, Katja Weisel, MD, of University Hospital Tubingen in Germany, addresses the barriers to longer treatment in patients with multiple myeloma.

Attitudes regarding longer treatment can present barriers to widespread adoption of this approach in multiple myeloma (MM).

Indeed, some clinicians continue to follow a fixed-duration approach to treatment in MM, only considering further treatment once the patient has relapsed rather than treating the patient until disease progression.

In the MM community, some are reluctant to adopt a strategy of treating longer because of the modest efficacy gains observed with early research or concern over tolerability issues, including the risk of developing peripheral neuropathy or secondary malignancies.¹

Others are uncertain about the optimal duration of therapy or the selection of an agent that will balance any potential gain in depth of response with the risk of late-onset or cumulative toxicities.

The potentially high cost of longer treatment for patients, their families, and/or the healthcare system overall also presents a challenge.

It is feasible that treating patients for longer may drive up healthcare utilization and take a toll on patients and caregivers, who may incur out-of-pocket costs because of the need to travel to a hospital or doctor’s office for intravenous therapies, requiring them to miss work.²

It is important to recognize, however, that more convenient all-oral treatment regimens are now available that do not require infusion at a hospital or clinic. Furthermore, results from recent studies suggest the majority of cancer patients prefer oral over intravenous therapies, which could reduce non-pharmacy healthcare costs.^3,4

Healthcare providers might be more likely to accept and adopt a longer treatment approach for MM if they had access to data describing the optimal duration, dosage, schedule, toxicity, and quality of life standards.

Ongoing, randomized, phase 3 trials are evaluating the benefits of treating longer with an oral proteasome inhibitor in patients with newly diagnosed MM.^5,6

Updated treatment guidelines and consensus statements will provide further guidance for clinicians on the benefits of maintenance therapy in both transplant-eligible and -ineligible patients with newly diagnosed MM.

The recently updated MM guidelines from the European Society for Medical Oncology (ESMO) recommend longer treatment or maintenance therapy in patients who have undergone hematopoietic stem cell transplant (HSCT).⁷

Based on evidence from studies such as FIRST and SWOG S0777, ESMO also recommends continuous treatment or treatment until progression with lenalidomide-dexamethasone and bortezomib-lenalidomide-dexamethasone in MM patients who are ineligible for HSCT.^7-9

As there is no one-size-fits-all treatment approach in MM, a personalized treatment plan should be designed for each patient. This plan should take into account a number of factors, including age, disease characteristics, performance status, treatment history, and the patient’s goals of care and personal preferences.¹⁰

If the patient is a candidate for longer treatment, the clinician should carefully weigh the potential impact on disease-free and overall survival against the potential side effects, as well as assess the patient’s likelihood of adhering to the medication.

With the availability of newer, less-toxic medications that can be tolerated for a greater duration and are easy to administer, aiding in overall treatment compliance, sustained remissions are possible.^11-13

Forty years ago, MM patients had very few treatment options, and the 5-year survival rate was 26%.¹⁴

Since then, novel therapies, including proteasome inhibitors and immunomodulatory drugs, have replaced conventional cytotoxic chemotherapy, leading to major improvements in survival.^15,16

With emerging research that supports the value of longer treatment strategies for both patients and the healthcare system, clinicians will have a proven strategy to help their patients attain long-term disease control while maintaining quality of life.^{2, 17-19} 

Dr. Weisel has received honoraria and/or consultancy fees from Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda. She has received research funding from Amgen, Celgene, Sanofi, and Janssen.

 The W2O Group provided writing support for this editorial, which was funded by Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

1.  Lipe B et al. Blood Cancer J. 2016; 6(10): e485. doi:  10.1038/bcj.2016.89

2.   Goodwin J et al. Cancer Nurs. 2013; 36(4):301-8. doi: 10.1097/NCC.0b013e3182693522

3.   Eek D et al. Patient Prefer Adherence. 2016; 10:1609-21. doi: 10.2147/PPA.S106629

4.   Bauer S et al. Value in Health. 2017; 20: A451. Abstract PCN217. doi: https://doi.org/10.1016/j.jval.2017.08.299

5.   A Study of Oral Ixazomib Citrate (MLN9708) Maintenance Therapy in Participants With Multiple Myeloma Following Autologous Stem Cell Transplant. (2014). Retrieved from https://clinicaltrials.gov/ct2/show/NCT02181413 (Identification No. NCT02181413).

6.   A Study of Oral Ixazomib Maintenance Therapy in Patients With Newly Diagnosed Multiple Myeloma Not Treated With Stem Cell Transplantation. (2014). Retrieved from https://clinicaltrials.gov/ct2/show/NCT02312258 (Identification No. NCT02312258).

7. Moreau P et al. Ann Oncol. 2017; 28: iv52-iv61. doi: https://org/10.1093/annonc/mdx096

8.   Facon T et al. Blood. 2018131(3):301-310. doi: 10.1182/blood-2017-07-795047

9.   Durie BG et al. Lancet. 2017; 389(10068):519-527. doi: 10.1016/S0140-6736(16)31594-X.

10.  Laubach J et al. Leukemia. 2016; 30(5):1005-17. doi: 10.1038/leu.2015.356

11.  Ludwig H et al. Blood. 2012; 119: 3003-3015. doi: https://doi.org/10.1182/blood-2011-11-374249

12.  Lehners N et al. Cancer Med. 2018; 7(2): 307–316. doi: 10.1002/cam4.1283

13.  Attal M et al. N Engl J Med. 2012; 366:1872-1791. doi: 10.1056/NEJMoa1114138

14.  National Cancer Institute. SEER Cancer Statistics Review (CSR) 1975-2014. National Cancer Institute. https://seer.cancer.gov/csr/1975_2014/. Accessed March 28, 2018.

15.  Kumar SK et al. Blood. 2008 Mar 1;111(5):2516-20. doi: 10.1182/blood-2007-10-116129

16.  Fonseca R et al. Leukemia. 2017 Sep;31(9):1915-1921. doi: 10.1038/leu.2016.380

17.  Palumbo A, Niesvizky R. Leuk Res. 2012; 36 Suppl 1:S19-26. doi: 10.1016/S0145-2126(12)70005-X

18.  Girnius S, Munshi NC. Leuk Suppl. 2013; 2(Suppl 1): S3–S9. doi:  10.1038/leusup.2013.2

19.  Mateos M-V, San Miguel JF. Hematology Am Soc Hematol Educ Program. 2013; 2013:488-95. doi: 10.1182/asheducation-2013.1.488

About one in seven patients with newly diagnosed multiple myeloma who are eligible for transplant are living at least as long as similar individuals in the general population, finds a retrospective cohort study of the International Myeloma Working Group. That figure may be even higher today because more than 90% of patients in the study – the largest yet to look at outcome predictors in this population – were treated in the era before novel therapies became available.

Investigators led by Saad Z. Usmani, MD, director/chief of plasma cell disorders and director of clinical research (hematologic malignancies) at the Levine Cancer Institute/Atrium Health in Charlotte, N.C., studied 7,291 patients with newly diagnosed multiple myeloma who were up to 75 years old and eligible for high-dose melphalan and autologous stem cell transplant. The patients were treated in clinical trials in 10 countries.

Compared with counterparts who did not achieve complete response 1 year after diagnosis, patients who did had better median progression-free survival (3.3 vs. 2.6 years; P less than .0001) and median overall survival (8.5 vs. 6.3 years; P less than .0001), according to study results report in Blood Cancer Journal.

The investigators next performed multivariate analyses to assess clinical variables at diagnosis associated with 10-year survival as compared with 2-year death.

Results here indicated that patients were less likely to be alive at 10 years if they were older than 65 years (odds ratio for death, 1.87; P = .002); had an immunoglobulin A isotype (OR, 1.53; P = .004); had a low albumin level, defined as less than 3.5 g/dL (OR, 1.36; P = .023); had an elevated beta₂-microglobulin level, defined as at least 3.5 mg/dL (OR, 1.86; P less than .001); had a higher serum creatinine level, defined as at least 2 mg/dL (OR, 1.77; P = .005); had a lower hemoglobin level, defined as less than 10 g/dL (OR, 1.55; P = .003); or had a lower platelet count, defined as less than 150,000/μL (OR, 2.26; P less than .001).

Cytogenetic abnormalities did not independently predict long-term survival, but these abnormalities were obtained only by conventional band karyotyping and were not available for some patients.

Overall, the cohort had a relative survival of about 0.9 when compared with the matched general population. With follow-up out to about 20 years, the cure fraction (proportion achieving or exceeding expected survival when compared with the matched general population) was 14.3%.

Identification of early complete response as a predictor of long-term survival “underscores the importance of depth of response as we explore novel regimens for newly diagnosed [multiple myeloma] along with [minimal residual disease] endpoints,” Dr. Usmani and his colleagues wrote while acknowledging that the patients studied were a selected group eligible for transplant and treated on trials.

Recent therapeutic advances “have reignited the debate on possible functional curability of a subset MM patients,” they noted. “[T]here are perhaps more effective drugs and drug classes in the clinician’s armamentarium than [were] available for MM patients being treated in the 1990s or even early 2000s. This may mean that the depth of response after induction therapy may continue to improve over time, potentially further improving the PFS/OS of [the] biologic subset who previously achieved [partial response] yet had good long-term survival.”

Dr. Usmani disclosed that he is a consultant for AbbVie, Amgen, BMS, Celgene, Janssen, Takeda, Sanofi, and SkylineDx; receives speaker’s fees for Amgen, Celgene, Janssen, and Takeda; and receives research funding from Amgen, Array Biopharma, BMS, Celgene, Janssen, Pharmacyclics, Sanofi, and Takeda.

SOURCE: Usmani SZ et al. Blood Cancer J. 2018 Nov 23;8(12):123..






 

About one in seven patients with newly diagnosed multiple myeloma who are eligible for transplant are living at least as long as similar individuals in the general population, finds a retrospective cohort study of the International Myeloma Working Group. That figure may be even higher today because more than 90% of patients in the study – the largest yet to look at outcome predictors in this population – were treated in the era before novel therapies became available.

Investigators led by Saad Z. Usmani, MD, director/chief of plasma cell disorders and director of clinical research (hematologic malignancies) at the Levine Cancer Institute/Atrium Health in Charlotte, N.C., studied 7,291 patients with newly diagnosed multiple myeloma who were up to 75 years old and eligible for high-dose melphalan and autologous stem cell transplant. The patients were treated in clinical trials in 10 countries.

Compared with counterparts who did not achieve complete response 1 year after diagnosis, patients who did had better median progression-free survival (3.3 vs. 2.6 years; P less than .0001) and median overall survival (8.5 vs. 6.3 years; P less than .0001), according to study results report in Blood Cancer Journal.

The investigators next performed multivariate analyses to assess clinical variables at diagnosis associated with 10-year survival as compared with 2-year death.

Results here indicated that patients were less likely to be alive at 10 years if they were older than 65 years (odds ratio for death, 1.87; P = .002); had an immunoglobulin A isotype (OR, 1.53; P = .004); had a low albumin level, defined as less than 3.5 g/dL (OR, 1.36; P = .023); had an elevated beta₂-microglobulin level, defined as at least 3.5 mg/dL (OR, 1.86; P less than .001); had a higher serum creatinine level, defined as at least 2 mg/dL (OR, 1.77; P = .005); had a lower hemoglobin level, defined as less than 10 g/dL (OR, 1.55; P = .003); or had a lower platelet count, defined as less than 150,000/μL (OR, 2.26; P less than .001).

Cytogenetic abnormalities did not independently predict long-term survival, but these abnormalities were obtained only by conventional band karyotyping and were not available for some patients.

Overall, the cohort had a relative survival of about 0.9 when compared with the matched general population. With follow-up out to about 20 years, the cure fraction (proportion achieving or exceeding expected survival when compared with the matched general population) was 14.3%.

Identification of early complete response as a predictor of long-term survival “underscores the importance of depth of response as we explore novel regimens for newly diagnosed [multiple myeloma] along with [minimal residual disease] endpoints,” Dr. Usmani and his colleagues wrote while acknowledging that the patients studied were a selected group eligible for transplant and treated on trials.

Recent therapeutic advances “have reignited the debate on possible functional curability of a subset MM patients,” they noted. “[T]here are perhaps more effective drugs and drug classes in the clinician’s armamentarium than [were] available for MM patients being treated in the 1990s or even early 2000s. This may mean that the depth of response after induction therapy may continue to improve over time, potentially further improving the PFS/OS of [the] biologic subset who previously achieved [partial response] yet had good long-term survival.”

Dr. Usmani disclosed that he is a consultant for AbbVie, Amgen, BMS, Celgene, Janssen, Takeda, Sanofi, and SkylineDx; receives speaker’s fees for Amgen, Celgene, Janssen, and Takeda; and receives research funding from Amgen, Array Biopharma, BMS, Celgene, Janssen, Pharmacyclics, Sanofi, and Takeda.

SOURCE: Usmani SZ et al. Blood Cancer J. 2018 Nov 23;8(12):123..






 

About one in seven patients with newly diagnosed multiple myeloma who are eligible for transplant are living at least as long as similar individuals in the general population, finds a retrospective cohort study of the International Myeloma Working Group. That figure may be even higher today because more than 90% of patients in the study – the largest yet to look at outcome predictors in this population – were treated in the era before novel therapies became available.

Investigators led by Saad Z. Usmani, MD, director/chief of plasma cell disorders and director of clinical research (hematologic malignancies) at the Levine Cancer Institute/Atrium Health in Charlotte, N.C., studied 7,291 patients with newly diagnosed multiple myeloma who were up to 75 years old and eligible for high-dose melphalan and autologous stem cell transplant. The patients were treated in clinical trials in 10 countries.

Compared with counterparts who did not achieve complete response 1 year after diagnosis, patients who did had better median progression-free survival (3.3 vs. 2.6 years; P less than .0001) and median overall survival (8.5 vs. 6.3 years; P less than .0001), according to study results report in Blood Cancer Journal.

The investigators next performed multivariate analyses to assess clinical variables at diagnosis associated with 10-year survival as compared with 2-year death.

Results here indicated that patients were less likely to be alive at 10 years if they were older than 65 years (odds ratio for death, 1.87; P = .002); had an immunoglobulin A isotype (OR, 1.53; P = .004); had a low albumin level, defined as less than 3.5 g/dL (OR, 1.36; P = .023); had an elevated beta₂-microglobulin level, defined as at least 3.5 mg/dL (OR, 1.86; P less than .001); had a higher serum creatinine level, defined as at least 2 mg/dL (OR, 1.77; P = .005); had a lower hemoglobin level, defined as less than 10 g/dL (OR, 1.55; P = .003); or had a lower platelet count, defined as less than 150,000/μL (OR, 2.26; P less than .001).

Cytogenetic abnormalities did not independently predict long-term survival, but these abnormalities were obtained only by conventional band karyotyping and were not available for some patients.

Overall, the cohort had a relative survival of about 0.9 when compared with the matched general population. With follow-up out to about 20 years, the cure fraction (proportion achieving or exceeding expected survival when compared with the matched general population) was 14.3%.

Identification of early complete response as a predictor of long-term survival “underscores the importance of depth of response as we explore novel regimens for newly diagnosed [multiple myeloma] along with [minimal residual disease] endpoints,” Dr. Usmani and his colleagues wrote while acknowledging that the patients studied were a selected group eligible for transplant and treated on trials.

Recent therapeutic advances “have reignited the debate on possible functional curability of a subset MM patients,” they noted. “[T]here are perhaps more effective drugs and drug classes in the clinician’s armamentarium than [were] available for MM patients being treated in the 1990s or even early 2000s. This may mean that the depth of response after induction therapy may continue to improve over time, potentially further improving the PFS/OS of [the] biologic subset who previously achieved [partial response] yet had good long-term survival.”

Dr. Usmani disclosed that he is a consultant for AbbVie, Amgen, BMS, Celgene, Janssen, Takeda, Sanofi, and SkylineDx; receives speaker’s fees for Amgen, Celgene, Janssen, and Takeda; and receives research funding from Amgen, Array Biopharma, BMS, Celgene, Janssen, Pharmacyclics, Sanofi, and Takeda.

SOURCE: Usmani SZ et al. Blood Cancer J. 2018 Nov 23;8(12):123..






 

© Todd Buchanan 2017

An additional presentation has been added to the late-breaking abstract session of the 2018 ASH Annual Meeting.

The session was expanded from six abstracts to seven this year because of a record number of “exciting” submissions, according to ASH Secretary Robert A. Brodsky, MD, of Johns Hopkins University in Baltimore, Maryland.

“We received 98 late-breaking abstracts, which is a record,” Dr. Brodsky said.

“They were so exciting this year that we added a seventh, and, quite frankly, we could have added several more, but we just didn’t have time in the meeting.”

Dr. Brodsky discussed this year’s late-breaking abstracts during a recent press briefing.

Abstract LBA-1 reports results of rivaroxaban thromboprophylaxis in cancer patients with an increased risk of venous thromboembolism (VTE). Compared to placebo, rivaroxaban significantly reduced VTE and VTE-related death during treatment but not over the entire study period.

Abstract LBA-2 describes a phase 3, randomized trial comparing daratumumab plus lenalidomide and dexamethasone to lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma who are ineligible for transplant. The addition of daratumumab reduced the risk of disease progression or death by 45%.

Abstract LBA-3 details results with HemoTypeSC, a test used to detect sickle cell trait and sickle cell disease. The test correctly identified all phenotypes in the 1,000 children studied.

Abstract LBA-4 describes a randomized, phase 3 study comparing ibrutinib plus rituximab to fludarabine, cyclophosphamide, and rituximab in younger patients with untreated chronic lymphocytic leukemia (CLL). Investigators found that ibrutinib plus rituximab provided significantly better progression-free and overall survival than the three-drug combination.

Abstract LBA-5 details a strategy for direct oral anticoagulant use in patients with atrial fibrillation undergoing surgery. Investigators say the strategy is likely to be “practice-changing” and incorporated into guidelines.

Abstract LBA-6 ­covers a trial of emapalumab in patients with primary hemophagocytic lymphohistiocytosis. Emapalumab, which was recently approved by the U.S. Food and Drug Administration, produced responses in most of the 34 patients studied and had a favorable safety profile, according to investigators.

Abstract LBA-7 reports the discovery of a recurrent mutation in BCL2 that confers resistance to venetoclax in patients with progressive CLL. Investigators say this mutation could be a biomarker of CLL relapse.

© Todd Buchanan 2017

An additional presentation has been added to the late-breaking abstract session of the 2018 ASH Annual Meeting.

The session was expanded from six abstracts to seven this year because of a record number of “exciting” submissions, according to ASH Secretary Robert A. Brodsky, MD, of Johns Hopkins University in Baltimore, Maryland.

“We received 98 late-breaking abstracts, which is a record,” Dr. Brodsky said.

“They were so exciting this year that we added a seventh, and, quite frankly, we could have added several more, but we just didn’t have time in the meeting.”

Dr. Brodsky discussed this year’s late-breaking abstracts during a recent press briefing.

Abstract LBA-1 reports results of rivaroxaban thromboprophylaxis in cancer patients with an increased risk of venous thromboembolism (VTE). Compared to placebo, rivaroxaban significantly reduced VTE and VTE-related death during treatment but not over the entire study period.

Abstract LBA-2 describes a phase 3, randomized trial comparing daratumumab plus lenalidomide and dexamethasone to lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma who are ineligible for transplant. The addition of daratumumab reduced the risk of disease progression or death by 45%.

Abstract LBA-3 details results with HemoTypeSC, a test used to detect sickle cell trait and sickle cell disease. The test correctly identified all phenotypes in the 1,000 children studied.

Abstract LBA-4 describes a randomized, phase 3 study comparing ibrutinib plus rituximab to fludarabine, cyclophosphamide, and rituximab in younger patients with untreated chronic lymphocytic leukemia (CLL). Investigators found that ibrutinib plus rituximab provided significantly better progression-free and overall survival than the three-drug combination.

Abstract LBA-5 details a strategy for direct oral anticoagulant use in patients with atrial fibrillation undergoing surgery. Investigators say the strategy is likely to be “practice-changing” and incorporated into guidelines.

Abstract LBA-6 ­covers a trial of emapalumab in patients with primary hemophagocytic lymphohistiocytosis. Emapalumab, which was recently approved by the U.S. Food and Drug Administration, produced responses in most of the 34 patients studied and had a favorable safety profile, according to investigators.

Abstract LBA-7 reports the discovery of a recurrent mutation in BCL2 that confers resistance to venetoclax in patients with progressive CLL. Investigators say this mutation could be a biomarker of CLL relapse.

© Todd Buchanan 2017

An additional presentation has been added to the late-breaking abstract session of the 2018 ASH Annual Meeting.

The session was expanded from six abstracts to seven this year because of a record number of “exciting” submissions, according to ASH Secretary Robert A. Brodsky, MD, of Johns Hopkins University in Baltimore, Maryland.

“We received 98 late-breaking abstracts, which is a record,” Dr. Brodsky said.

“They were so exciting this year that we added a seventh, and, quite frankly, we could have added several more, but we just didn’t have time in the meeting.”

Dr. Brodsky discussed this year’s late-breaking abstracts during a recent press briefing.

Abstract LBA-1 reports results of rivaroxaban thromboprophylaxis in cancer patients with an increased risk of venous thromboembolism (VTE). Compared to placebo, rivaroxaban significantly reduced VTE and VTE-related death during treatment but not over the entire study period.

Abstract LBA-2 describes a phase 3, randomized trial comparing daratumumab plus lenalidomide and dexamethasone to lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma who are ineligible for transplant. The addition of daratumumab reduced the risk of disease progression or death by 45%.

Abstract LBA-3 details results with HemoTypeSC, a test used to detect sickle cell trait and sickle cell disease. The test correctly identified all phenotypes in the 1,000 children studied.

Abstract LBA-4 describes a randomized, phase 3 study comparing ibrutinib plus rituximab to fludarabine, cyclophosphamide, and rituximab in younger patients with untreated chronic lymphocytic leukemia (CLL). Investigators found that ibrutinib plus rituximab provided significantly better progression-free and overall survival than the three-drug combination.

Abstract LBA-5 details a strategy for direct oral anticoagulant use in patients with atrial fibrillation undergoing surgery. Investigators say the strategy is likely to be “practice-changing” and incorporated into guidelines.

Abstract LBA-6 ­covers a trial of emapalumab in patients with primary hemophagocytic lymphohistiocytosis. Emapalumab, which was recently approved by the U.S. Food and Drug Administration, produced responses in most of the 34 patients studied and had a favorable safety profile, according to investigators.

Abstract LBA-7 reports the discovery of a recurrent mutation in BCL2 that confers resistance to venetoclax in patients with progressive CLL. Investigators say this mutation could be a biomarker of CLL relapse.

Micrograph showing MM

A retrospective study suggests haploidentical hematopoietic stem cell transplant (haplo-HSCT) is feasible in patients with multiply relapsed or high-risk multiple myeloma (MM).

Investigators said haplo-HSCT produced an “acceptable” rate of non-relapse mortality (NRM)—21% at 1 year—in such patients.

“Our results demonstrate that [haplo-HSCT] can be safely performed in appropriate patients with MM who lack an HLA-matched sibling or unrelated donor,” the investigators wrote in Biology of Blood and Marrow Transplantation.

The research was conducted by Firoozeh Sahebi, MD, of City of Hope Medical Center in Duarte, California, and her colleagues.

The team analyzed data from 96 MM patients who had failed at least one previous autologous transplant and underwent haplo-HSCT between 2008 and 2016.

The patients had a median age of 54.9 (range, 36.6-73.3), and 65.6% were male. At baseline, 37.5% of patients were in very good partial response or better, 31.2% were in partial response, 13.5% had stable disease, and 17.7% had relapsed disease.

The median follow-up was 24 months. Almost all patients (97%) achieved neutrophil engraftment by day 28, and 75% had recovery of platelets by day 60.

Grade 2-4 acute graft-vs-host-disease occurred in 39% of patients by 100 days. Chronic graft-vs-host-disease was seen in 46% of patients at 2 years.

The rate of NRM was 21% at 1 year and 26% at 2 years. The cumulative risk of relapse and progression was 50% at 1 year and 56% at 2 years.

The 2-year progression-free survival (PFS) was 17%, and the 2-year overall survival (OS) was 48%.

In a univariate analysis, bone marrow transplant was associated with significantly better OS than peripheral blood transplant (P=0.001). However, there was no significant difference in PFS between the two.

NRM was lower with bone marrow transplant (P=0.016), and there was a trend toward a higher relapse rate with bone marrow (P=0.083).

The use of cyclophosphamide after transplant was associated with significantly better OS (P=0.009) but not PFS, NRM, or relapse.

Other factors—such as disease status and conditioning regimen—had no significant impact on survival, NRM, or relapse.

The investigators said they had no conflicts of interest related to this research.

Micrograph showing MM

A retrospective study suggests haploidentical hematopoietic stem cell transplant (haplo-HSCT) is feasible in patients with multiply relapsed or high-risk multiple myeloma (MM).

Investigators said haplo-HSCT produced an “acceptable” rate of non-relapse mortality (NRM)—21% at 1 year—in such patients.

“Our results demonstrate that [haplo-HSCT] can be safely performed in appropriate patients with MM who lack an HLA-matched sibling or unrelated donor,” the investigators wrote in Biology of Blood and Marrow Transplantation.

The research was conducted by Firoozeh Sahebi, MD, of City of Hope Medical Center in Duarte, California, and her colleagues.

The team analyzed data from 96 MM patients who had failed at least one previous autologous transplant and underwent haplo-HSCT between 2008 and 2016.

The patients had a median age of 54.9 (range, 36.6-73.3), and 65.6% were male. At baseline, 37.5% of patients were in very good partial response or better, 31.2% were in partial response, 13.5% had stable disease, and 17.7% had relapsed disease.

The median follow-up was 24 months. Almost all patients (97%) achieved neutrophil engraftment by day 28, and 75% had recovery of platelets by day 60.

Grade 2-4 acute graft-vs-host-disease occurred in 39% of patients by 100 days. Chronic graft-vs-host-disease was seen in 46% of patients at 2 years.

The rate of NRM was 21% at 1 year and 26% at 2 years. The cumulative risk of relapse and progression was 50% at 1 year and 56% at 2 years.

The 2-year progression-free survival (PFS) was 17%, and the 2-year overall survival (OS) was 48%.

In a univariate analysis, bone marrow transplant was associated with significantly better OS than peripheral blood transplant (P=0.001). However, there was no significant difference in PFS between the two.

NRM was lower with bone marrow transplant (P=0.016), and there was a trend toward a higher relapse rate with bone marrow (P=0.083).

The use of cyclophosphamide after transplant was associated with significantly better OS (P=0.009) but not PFS, NRM, or relapse.

Other factors—such as disease status and conditioning regimen—had no significant impact on survival, NRM, or relapse.

The investigators said they had no conflicts of interest related to this research.

Micrograph showing MM

A retrospective study suggests haploidentical hematopoietic stem cell transplant (haplo-HSCT) is feasible in patients with multiply relapsed or high-risk multiple myeloma (MM).

Investigators said haplo-HSCT produced an “acceptable” rate of non-relapse mortality (NRM)—21% at 1 year—in such patients.

“Our results demonstrate that [haplo-HSCT] can be safely performed in appropriate patients with MM who lack an HLA-matched sibling or unrelated donor,” the investigators wrote in Biology of Blood and Marrow Transplantation.

The research was conducted by Firoozeh Sahebi, MD, of City of Hope Medical Center in Duarte, California, and her colleagues.

The team analyzed data from 96 MM patients who had failed at least one previous autologous transplant and underwent haplo-HSCT between 2008 and 2016.

The patients had a median age of 54.9 (range, 36.6-73.3), and 65.6% were male. At baseline, 37.5% of patients were in very good partial response or better, 31.2% were in partial response, 13.5% had stable disease, and 17.7% had relapsed disease.

The median follow-up was 24 months. Almost all patients (97%) achieved neutrophil engraftment by day 28, and 75% had recovery of platelets by day 60.

Grade 2-4 acute graft-vs-host-disease occurred in 39% of patients by 100 days. Chronic graft-vs-host-disease was seen in 46% of patients at 2 years.

The rate of NRM was 21% at 1 year and 26% at 2 years. The cumulative risk of relapse and progression was 50% at 1 year and 56% at 2 years.

The 2-year progression-free survival (PFS) was 17%, and the 2-year overall survival (OS) was 48%.

In a univariate analysis, bone marrow transplant was associated with significantly better OS than peripheral blood transplant (P=0.001). However, there was no significant difference in PFS between the two.

NRM was lower with bone marrow transplant (P=0.016), and there was a trend toward a higher relapse rate with bone marrow (P=0.083).

The use of cyclophosphamide after transplant was associated with significantly better OS (P=0.009) but not PFS, NRM, or relapse.

Other factors—such as disease status and conditioning regimen—had no significant impact on survival, NRM, or relapse.

The investigators said they had no conflicts of interest related to this research.

In the closest thing the medical world has to movie trailers, the American Society of Hematology held a press conference offering a peek into the much anticipated (and much hyped) clinical and research abstracts that will be presented at the 2018 ASH annual meeting.

Shorter R-CHOP regimen for DLBCL

Under the heading “Big Trials, Big Results” will be data from the FLYER trial, a phase 3, randomized, deescalation trial in 592 patients aged 18-60 years with favorable-prognosis diffuse large B-cell lymphoma. The investigators report that both progression-free survival and overall survival with four cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone) were noninferior to those for patients treated with six cycles of R-CHOP (abstract 781).

Ibrutinib mastery in CLL

Also on the program are results of a study showing that ibrutinib (Imbruvica), either alone or in combination with rituximab, is associated with superior progression-free survival than bendamustine and rituximab in older patients with chronic lymphocytic leukemia (CLL).

The trial, the Alliance North American Intergroup Study A041202 (abstract 6) is the first major trial to pit ibrutinib against the modern standard of immunochemotherapy rather than the older standard of chlorambucil, Dr. Brodsky noted.

Anemia support in beta-thalassemia, MDS

In nonmalignant disease, investigators in the randomized, phase 3 BELIEVE trial are reporting results of their study showing that the first-in-class erythroid maturation agent luspatercept was associated with significant reductions in the need for RBC transfusion in adults with transfusion-dependent beta-thalassemia.

The investigators report that the experimental agent was “generally well tolerated” (abstract 163).

“Beyond a proof of principle, [this is] certainly a very exciting advancement in this group of patients who otherwise had very few treatment options,” said Alexis A. Thompson, MD, associate director of equity and minority health at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, and the current ASH president.

Dr. Thompson also highlighted the MEDALIST trial (abstract 1), a phase 3, randomized study showing that luspatercept significantly reduced transfusion burden, compared with placebo, in patients with anemia caused by very low–, low-, or intermediate-risk myelodysplastic syndrome with ring sideroblasts who require RBC transfusions.

“This group of patients were individuals who were refractory or were not responders or did not tolerate erythropoietic stimulating agents and therefore were requiring regular transfusion,” Dr. Thompson said.

Worth the wait

The late-breaking abstract program was stretched from the usual six abstracts to seven this year because of the unusually high quality of the science, Dr. Brodsky said.

Among these star attractions are results of a phase 3, randomized study of daratumumab (Darzalex) plus lenalidomide and dexamethasone versus lenalidomide-dexamethasone alone for patients with newly diagnosed multiple myeloma who are ineligible for transplant.

The investigators found that adding daratumumab reduced the risk of disease progression or death by close to 50%, supporting the combination as a new standard of care in these patients, according to Thierry Facon, MD, from the Hospital Claude Huriez in Lille, France, and colleagues (abstract LBA-2).

Two other late-breakers deal with CLL. The first, a randomized, phase 3 study of ibrutinib-based therapy versus standard fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy in younger patients with untreated CLL, found that ibrutinib and rituximab provided significantly better progression-free survival and overall survival (abstract LBA-4).

“These findings have immediate practice-changing implications and establish ibrutinib-based therapy as the most efficacious first-line therapy for patients with CLL,” wrote Tait D. Shanafelt, MD, from Stanford (Calif.) University, and colleagues.

On a less positive note, Australian researchers report their discovery of a recurrent mutation in BCL2 that confers resistance to venetoclax (Venclexta) in patients with progressive CLL (abstract LBA-7).

“This mutation provides new insights into the pathobiology of venetoclax resistance and provides a potential biomarker of impending clinical relapse,” wrote Piers Blombery, MBBS, from the University of Melbourne, and colleagues.

Finally, investigators from children’s hospitals in the United States and Europe report promising findings on the safety and efficacy of emapalumab for the treatment of patients with the rare genetic disorder primary hemophagocytic lymphohistiocytosis (HLH).

The drug, newly approved by the Food and Drug Administration, was able to control HLH’s hyperinflammatory activity, and allowed a substantial proportion of patients to survive to hematopoietic stem cell transplantation, the investigators said (abstract LBA-6­).

In the closest thing the medical world has to movie trailers, the American Society of Hematology held a press conference offering a peek into the much anticipated (and much hyped) clinical and research abstracts that will be presented at the 2018 ASH annual meeting.

Shorter R-CHOP regimen for DLBCL

Under the heading “Big Trials, Big Results” will be data from the FLYER trial, a phase 3, randomized, deescalation trial in 592 patients aged 18-60 years with favorable-prognosis diffuse large B-cell lymphoma. The investigators report that both progression-free survival and overall survival with four cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone) were noninferior to those for patients treated with six cycles of R-CHOP (abstract 781).

Ibrutinib mastery in CLL

Also on the program are results of a study showing that ibrutinib (Imbruvica), either alone or in combination with rituximab, is associated with superior progression-free survival than bendamustine and rituximab in older patients with chronic lymphocytic leukemia (CLL).

The trial, the Alliance North American Intergroup Study A041202 (abstract 6) is the first major trial to pit ibrutinib against the modern standard of immunochemotherapy rather than the older standard of chlorambucil, Dr. Brodsky noted.

Anemia support in beta-thalassemia, MDS

In nonmalignant disease, investigators in the randomized, phase 3 BELIEVE trial are reporting results of their study showing that the first-in-class erythroid maturation agent luspatercept was associated with significant reductions in the need for RBC transfusion in adults with transfusion-dependent beta-thalassemia.

The investigators report that the experimental agent was “generally well tolerated” (abstract 163).

“Beyond a proof of principle, [this is] certainly a very exciting advancement in this group of patients who otherwise had very few treatment options,” said Alexis A. Thompson, MD, associate director of equity and minority health at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, and the current ASH president.

Dr. Thompson also highlighted the MEDALIST trial (abstract 1), a phase 3, randomized study showing that luspatercept significantly reduced transfusion burden, compared with placebo, in patients with anemia caused by very low–, low-, or intermediate-risk myelodysplastic syndrome with ring sideroblasts who require RBC transfusions.

“This group of patients were individuals who were refractory or were not responders or did not tolerate erythropoietic stimulating agents and therefore were requiring regular transfusion,” Dr. Thompson said.

Worth the wait

The late-breaking abstract program was stretched from the usual six abstracts to seven this year because of the unusually high quality of the science, Dr. Brodsky said.

Among these star attractions are results of a phase 3, randomized study of daratumumab (Darzalex) plus lenalidomide and dexamethasone versus lenalidomide-dexamethasone alone for patients with newly diagnosed multiple myeloma who are ineligible for transplant.

The investigators found that adding daratumumab reduced the risk of disease progression or death by close to 50%, supporting the combination as a new standard of care in these patients, according to Thierry Facon, MD, from the Hospital Claude Huriez in Lille, France, and colleagues (abstract LBA-2).

Two other late-breakers deal with CLL. The first, a randomized, phase 3 study of ibrutinib-based therapy versus standard fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy in younger patients with untreated CLL, found that ibrutinib and rituximab provided significantly better progression-free survival and overall survival (abstract LBA-4).

“These findings have immediate practice-changing implications and establish ibrutinib-based therapy as the most efficacious first-line therapy for patients with CLL,” wrote Tait D. Shanafelt, MD, from Stanford (Calif.) University, and colleagues.

On a less positive note, Australian researchers report their discovery of a recurrent mutation in BCL2 that confers resistance to venetoclax (Venclexta) in patients with progressive CLL (abstract LBA-7).

“This mutation provides new insights into the pathobiology of venetoclax resistance and provides a potential biomarker of impending clinical relapse,” wrote Piers Blombery, MBBS, from the University of Melbourne, and colleagues.

Finally, investigators from children’s hospitals in the United States and Europe report promising findings on the safety and efficacy of emapalumab for the treatment of patients with the rare genetic disorder primary hemophagocytic lymphohistiocytosis (HLH).

The drug, newly approved by the Food and Drug Administration, was able to control HLH’s hyperinflammatory activity, and allowed a substantial proportion of patients to survive to hematopoietic stem cell transplantation, the investigators said (abstract LBA-6­).

In the closest thing the medical world has to movie trailers, the American Society of Hematology held a press conference offering a peek into the much anticipated (and much hyped) clinical and research abstracts that will be presented at the 2018 ASH annual meeting.

Shorter R-CHOP regimen for DLBCL

Under the heading “Big Trials, Big Results” will be data from the FLYER trial, a phase 3, randomized, deescalation trial in 592 patients aged 18-60 years with favorable-prognosis diffuse large B-cell lymphoma. The investigators report that both progression-free survival and overall survival with four cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone) were noninferior to those for patients treated with six cycles of R-CHOP (abstract 781).

Ibrutinib mastery in CLL

Also on the program are results of a study showing that ibrutinib (Imbruvica), either alone or in combination with rituximab, is associated with superior progression-free survival than bendamustine and rituximab in older patients with chronic lymphocytic leukemia (CLL).

The trial, the Alliance North American Intergroup Study A041202 (abstract 6) is the first major trial to pit ibrutinib against the modern standard of immunochemotherapy rather than the older standard of chlorambucil, Dr. Brodsky noted.

Anemia support in beta-thalassemia, MDS

In nonmalignant disease, investigators in the randomized, phase 3 BELIEVE trial are reporting results of their study showing that the first-in-class erythroid maturation agent luspatercept was associated with significant reductions in the need for RBC transfusion in adults with transfusion-dependent beta-thalassemia.

The investigators report that the experimental agent was “generally well tolerated” (abstract 163).

“Beyond a proof of principle, [this is] certainly a very exciting advancement in this group of patients who otherwise had very few treatment options,” said Alexis A. Thompson, MD, associate director of equity and minority health at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, and the current ASH president.

Dr. Thompson also highlighted the MEDALIST trial (abstract 1), a phase 3, randomized study showing that luspatercept significantly reduced transfusion burden, compared with placebo, in patients with anemia caused by very low–, low-, or intermediate-risk myelodysplastic syndrome with ring sideroblasts who require RBC transfusions.

“This group of patients were individuals who were refractory or were not responders or did not tolerate erythropoietic stimulating agents and therefore were requiring regular transfusion,” Dr. Thompson said.

Worth the wait

The late-breaking abstract program was stretched from the usual six abstracts to seven this year because of the unusually high quality of the science, Dr. Brodsky said.

Among these star attractions are results of a phase 3, randomized study of daratumumab (Darzalex) plus lenalidomide and dexamethasone versus lenalidomide-dexamethasone alone for patients with newly diagnosed multiple myeloma who are ineligible for transplant.

The investigators found that adding daratumumab reduced the risk of disease progression or death by close to 50%, supporting the combination as a new standard of care in these patients, according to Thierry Facon, MD, from the Hospital Claude Huriez in Lille, France, and colleagues (abstract LBA-2).

Two other late-breakers deal with CLL. The first, a randomized, phase 3 study of ibrutinib-based therapy versus standard fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy in younger patients with untreated CLL, found that ibrutinib and rituximab provided significantly better progression-free survival and overall survival (abstract LBA-4).

“These findings have immediate practice-changing implications and establish ibrutinib-based therapy as the most efficacious first-line therapy for patients with CLL,” wrote Tait D. Shanafelt, MD, from Stanford (Calif.) University, and colleagues.

On a less positive note, Australian researchers report their discovery of a recurrent mutation in BCL2 that confers resistance to venetoclax (Venclexta) in patients with progressive CLL (abstract LBA-7).

“This mutation provides new insights into the pathobiology of venetoclax resistance and provides a potential biomarker of impending clinical relapse,” wrote Piers Blombery, MBBS, from the University of Melbourne, and colleagues.

Finally, investigators from children’s hospitals in the United States and Europe report promising findings on the safety and efficacy of emapalumab for the treatment of patients with the rare genetic disorder primary hemophagocytic lymphohistiocytosis (HLH).

The drug, newly approved by the Food and Drug Administration, was able to control HLH’s hyperinflammatory activity, and allowed a substantial proportion of patients to survive to hematopoietic stem cell transplantation, the investigators said (abstract LBA-6­).

Photo courtesy of the CDC

Phase 2 results suggest a three-drug regimen may improve response rates in patients with proteasome inhibitor (PI)-refractory multiple myeloma (MM).

The combination—nelfinavir, bortezomib, and dexamethasone (NeVd)—produced an objective response rate (ORR) of 65% in this trial.

In comparison, past studies have shown response rates of 24% to 36% in the PI-refractory MM population.^1,2,3

“The unprecedented ORR of NeVd observed in this heavily pretreated, multi-refractory setting warrants further investigation to explore the potential of nelfinavir in combination with PIs . . . ,” Christoph Driessen, of Kantonsspital St. Gallen in Switzerland, and his colleagues wrote in a letter to Blood.

The researchers noted that NeVd previously demonstrated activity in a phase 1 trial of MM patients who were refractory to both bortezomib and lenalidomide.

For the phase 2 study (NCT02188537), Dr. Driessen and his colleagues tested NeVd in MM patients who were refractory to their most recent PI-containing regimen and were previously exposed to or intolerant of at least one immunomodulatory drug.

The 34 patients had a median age of 67 (range, 42-82). Sixty-two percent were male, 38% had poor-risk cytogenetics, and most had a performance status of 0 (59%) or 1 (32%).

All patients had received lenalidomide, 47% had prior pomalidomide, 76% had prior high-dose chemotherapy, and 76% had a prior transplant.

All patients were bortezomib-refractory, 79% were refractory to a PI and lenalidomide, 44% were refractory to a PI and pomalidomide, and 38% were refractory to a PI, lenalidomide, and pomalidomide.

In this study, the patients received:

• Nelfinavir at 2500 mg on days 1 to 14 twice daily
• Bortezomib at 1.3 mg/m² subcutaneously on days 1, 4, 8, and 11
• Dexamethasone at 20 mg orally on days 1 to 2, 4 to 5, 8 to 9, and 11 to 12.

The patients were treated for up to six 21-day cycles. They received a median of 4.5 cycles (range, 1-6).

Results

The ORR was 65%, with 17 partial responses (PRs) and five very good PRs. Three patients had a minimal response, and four had stable disease.

The ORR (PR or better) was:

• 77% in patients with poor-risk cytogenetics
• 67% in patients with fewer than five prior therapies
• 63% in patients with five or more prior therapies
• 70% in patients refractory to bortezomib and lenalidomide
• 60% in patients refractory to bortezomib and pomalidomide
• 62% in patients refractory to bortezomib, lenalidomide, and pomalidomide.

The researchers said the clinical benefit of NeVd may have been underestimated in this trial because patients were only able to receive six cycles of treatment on study due to a lack of external funding support.

“The time course of paraprotein levels also suggests that individual patients might potentially have experienced myeloma control if NeVd had been continued until progression,” the researchers wrote.

Five patients did receive more than six cycles of NeVd on a compassionate-use basis. In all, 27 patients received additional anti-myeloma treatment during follow-up.

The median progression-free survival was 12 weeks for the entire cohort and 16 weeks among patients who achieved a PR or better.

The median overall survival was 12 months, and 17 patients had died as of November 2016.

The researchers said the most common adverse events in this trial were anemia (97%), thrombocytopenia (82%), hypertension (53%), diarrhea (47%), fatigue (38%), and dyspnea (35%).

There were four deaths during treatment—three due to septicemia and one from heart failure. Three of the deaths were associated with underlying pneumonia.

“Although this mortality rate is consistent with the background mortality among patients with heavily pretreated, refractory myeloma, these findings suggest that prophylactic antibiotic therapy should be considered in those with low neutrophil counts and/or advanced age undergoing NeVd treatment,” the researchers wrote.

This work was supported by the Swiss Group for Clinical Cancer Research, the Swiss State Secretariat for Education, Research and Innovation, the Rising Tide Foundation for Clinical Cancer Research, and the Gateway for Cancer Research.

Most of the researchers declared no competing financial interests, but one reported personal fees from Celgene, Takeda, Amgen, Novartis, and Janssen-Cilag that were unrelated to this trial.

1. Lokhorst HM et al. N Engl J Med. 2015; 373(13):1207-1219.

2. Dimopoulos MA et al. Blood. 2016;128(4): 497-503.

3. Siegel DS et al. Blood. 2012;120(14):2817-2825.

Photo courtesy of the CDC

Phase 2 results suggest a three-drug regimen may improve response rates in patients with proteasome inhibitor (PI)-refractory multiple myeloma (MM).

The combination—nelfinavir, bortezomib, and dexamethasone (NeVd)—produced an objective response rate (ORR) of 65% in this trial.

In comparison, past studies have shown response rates of 24% to 36% in the PI-refractory MM population.^1,2,3

“The unprecedented ORR of NeVd observed in this heavily pretreated, multi-refractory setting warrants further investigation to explore the potential of nelfinavir in combination with PIs . . . ,” Christoph Driessen, of Kantonsspital St. Gallen in Switzerland, and his colleagues wrote in a letter to Blood.

The researchers noted that NeVd previously demonstrated activity in a phase 1 trial of MM patients who were refractory to both bortezomib and lenalidomide.

For the phase 2 study (NCT02188537), Dr. Driessen and his colleagues tested NeVd in MM patients who were refractory to their most recent PI-containing regimen and were previously exposed to or intolerant of at least one immunomodulatory drug.

The 34 patients had a median age of 67 (range, 42-82). Sixty-two percent were male, 38% had poor-risk cytogenetics, and most had a performance status of 0 (59%) or 1 (32%).

All patients had received lenalidomide, 47% had prior pomalidomide, 76% had prior high-dose chemotherapy, and 76% had a prior transplant.

All patients were bortezomib-refractory, 79% were refractory to a PI and lenalidomide, 44% were refractory to a PI and pomalidomide, and 38% were refractory to a PI, lenalidomide, and pomalidomide.

In this study, the patients received:

• Nelfinavir at 2500 mg on days 1 to 14 twice daily
• Bortezomib at 1.3 mg/m² subcutaneously on days 1, 4, 8, and 11
• Dexamethasone at 20 mg orally on days 1 to 2, 4 to 5, 8 to 9, and 11 to 12.

The patients were treated for up to six 21-day cycles. They received a median of 4.5 cycles (range, 1-6).

Results

The ORR was 65%, with 17 partial responses (PRs) and five very good PRs. Three patients had a minimal response, and four had stable disease.

The ORR (PR or better) was:

• 77% in patients with poor-risk cytogenetics
• 67% in patients with fewer than five prior therapies
• 63% in patients with five or more prior therapies
• 70% in patients refractory to bortezomib and lenalidomide
• 60% in patients refractory to bortezomib and pomalidomide
• 62% in patients refractory to bortezomib, lenalidomide, and pomalidomide.

The researchers said the clinical benefit of NeVd may have been underestimated in this trial because patients were only able to receive six cycles of treatment on study due to a lack of external funding support.

“The time course of paraprotein levels also suggests that individual patients might potentially have experienced myeloma control if NeVd had been continued until progression,” the researchers wrote.

Five patients did receive more than six cycles of NeVd on a compassionate-use basis. In all, 27 patients received additional anti-myeloma treatment during follow-up.

The median progression-free survival was 12 weeks for the entire cohort and 16 weeks among patients who achieved a PR or better.

The median overall survival was 12 months, and 17 patients had died as of November 2016.

The researchers said the most common adverse events in this trial were anemia (97%), thrombocytopenia (82%), hypertension (53%), diarrhea (47%), fatigue (38%), and dyspnea (35%).

There were four deaths during treatment—three due to septicemia and one from heart failure. Three of the deaths were associated with underlying pneumonia.

“Although this mortality rate is consistent with the background mortality among patients with heavily pretreated, refractory myeloma, these findings suggest that prophylactic antibiotic therapy should be considered in those with low neutrophil counts and/or advanced age undergoing NeVd treatment,” the researchers wrote.

This work was supported by the Swiss Group for Clinical Cancer Research, the Swiss State Secretariat for Education, Research and Innovation, the Rising Tide Foundation for Clinical Cancer Research, and the Gateway for Cancer Research.

Most of the researchers declared no competing financial interests, but one reported personal fees from Celgene, Takeda, Amgen, Novartis, and Janssen-Cilag that were unrelated to this trial.

1. Lokhorst HM et al. N Engl J Med. 2015; 373(13):1207-1219.

2. Dimopoulos MA et al. Blood. 2016;128(4): 497-503.

3. Siegel DS et al. Blood. 2012;120(14):2817-2825.

Photo courtesy of the CDC

Phase 2 results suggest a three-drug regimen may improve response rates in patients with proteasome inhibitor (PI)-refractory multiple myeloma (MM).

The combination—nelfinavir, bortezomib, and dexamethasone (NeVd)—produced an objective response rate (ORR) of 65% in this trial.

In comparison, past studies have shown response rates of 24% to 36% in the PI-refractory MM population.^1,2,3

“The unprecedented ORR of NeVd observed in this heavily pretreated, multi-refractory setting warrants further investigation to explore the potential of nelfinavir in combination with PIs . . . ,” Christoph Driessen, of Kantonsspital St. Gallen in Switzerland, and his colleagues wrote in a letter to Blood.

The researchers noted that NeVd previously demonstrated activity in a phase 1 trial of MM patients who were refractory to both bortezomib and lenalidomide.

For the phase 2 study (NCT02188537), Dr. Driessen and his colleagues tested NeVd in MM patients who were refractory to their most recent PI-containing regimen and were previously exposed to or intolerant of at least one immunomodulatory drug.

The 34 patients had a median age of 67 (range, 42-82). Sixty-two percent were male, 38% had poor-risk cytogenetics, and most had a performance status of 0 (59%) or 1 (32%).

All patients had received lenalidomide, 47% had prior pomalidomide, 76% had prior high-dose chemotherapy, and 76% had a prior transplant.

All patients were bortezomib-refractory, 79% were refractory to a PI and lenalidomide, 44% were refractory to a PI and pomalidomide, and 38% were refractory to a PI, lenalidomide, and pomalidomide.

In this study, the patients received:

• Nelfinavir at 2500 mg on days 1 to 14 twice daily
• Bortezomib at 1.3 mg/m² subcutaneously on days 1, 4, 8, and 11
• Dexamethasone at 20 mg orally on days 1 to 2, 4 to 5, 8 to 9, and 11 to 12.

The patients were treated for up to six 21-day cycles. They received a median of 4.5 cycles (range, 1-6).

Results

The ORR was 65%, with 17 partial responses (PRs) and five very good PRs. Three patients had a minimal response, and four had stable disease.

The ORR (PR or better) was:

• 77% in patients with poor-risk cytogenetics
• 67% in patients with fewer than five prior therapies
• 63% in patients with five or more prior therapies
• 70% in patients refractory to bortezomib and lenalidomide
• 60% in patients refractory to bortezomib and pomalidomide
• 62% in patients refractory to bortezomib, lenalidomide, and pomalidomide.

The researchers said the clinical benefit of NeVd may have been underestimated in this trial because patients were only able to receive six cycles of treatment on study due to a lack of external funding support.

“The time course of paraprotein levels also suggests that individual patients might potentially have experienced myeloma control if NeVd had been continued until progression,” the researchers wrote.

Five patients did receive more than six cycles of NeVd on a compassionate-use basis. In all, 27 patients received additional anti-myeloma treatment during follow-up.

The median progression-free survival was 12 weeks for the entire cohort and 16 weeks among patients who achieved a PR or better.

The median overall survival was 12 months, and 17 patients had died as of November 2016.

The researchers said the most common adverse events in this trial were anemia (97%), thrombocytopenia (82%), hypertension (53%), diarrhea (47%), fatigue (38%), and dyspnea (35%).

There were four deaths during treatment—three due to septicemia and one from heart failure. Three of the deaths were associated with underlying pneumonia.

“Although this mortality rate is consistent with the background mortality among patients with heavily pretreated, refractory myeloma, these findings suggest that prophylactic antibiotic therapy should be considered in those with low neutrophil counts and/or advanced age undergoing NeVd treatment,” the researchers wrote.

This work was supported by the Swiss Group for Clinical Cancer Research, the Swiss State Secretariat for Education, Research and Innovation, the Rising Tide Foundation for Clinical Cancer Research, and the Gateway for Cancer Research.

Most of the researchers declared no competing financial interests, but one reported personal fees from Celgene, Takeda, Amgen, Novartis, and Janssen-Cilag that were unrelated to this trial.

1. Lokhorst HM et al. N Engl J Med. 2015; 373(13):1207-1219.

2. Dimopoulos MA et al. Blood. 2016;128(4): 497-503.

3. Siegel DS et al. Blood. 2012;120(14):2817-2825.

Photo by Junior Libby

A recent survey suggests Americans are nearly as worried about the cost of a cancer diagnosis as they are about dying from cancer.

The cost of cancer care was a top concern even among people who had no prior experience with cancer.

At the same time, cancer patients/survivors admitted to delaying or forgoing care due to costs, and caregivers reported taking “dramatic” actions to pay for their loved one’s care.

These are findings from the American Society of Clinical Oncology (ASCO)’s second annual National Cancer Opinion Survey.

The survey was conducted online by The Harris Poll from July 10, 2018, to August 10, 2018. It included 4,887 U.S. adults age 18 and older—1,001 of whom have or had cancer.

Cost among top concerns

Death and pain/suffering were the top concerns related to a cancer diagnosis. Fifty-four percent of respondents said death would be one of their greatest concerns if they were diagnosed with cancer, and the same percentage rated pain/suffering a top concern.

Forty-four percent of respondents said paying for cancer treatment would be a top concern, and 45% said the same about the financial impact of a cancer diagnosis on their family. When combined, financial issues were a top concern for 57% of respondents.

Paying for treatment was a top concern for:

• 36% of respondents who had/have cancer
• 51% of caregivers
• 43% of people with no prior cancer experience.

The financial impact on family was a top concern for:

• 39% of respondents who had/have cancer
• 55% of caregivers
• 42% of people with no prior cancer experience.

Cutting costs

Sixty-one percent of caregivers surveyed said they or another relative have taken a “dramatic” step to help pay for their loved one’s care, including:

• Dipping into savings accounts (35%)
• Working extra hours (23%)
• Taking an early withdrawal from a retirement account or college fund (14%)
• Postponing retirement (14%)
• Taking out a second mortgage or other type of loan (13%)
• Taking an additional job (13%)
• Selling family heirlooms (9%).

Twenty percent of cancer patients/survivors said they have taken actions to reduce treatment costs, including:

• Delaying scans (7%)
• Skipping or delaying appointments (7%)
• Skipping doses of prescribed treatment (6%)
• Postponing or not filling prescriptions (5%)
• Refusing treatment (3%).

“Patients are right to be concerned about the financial impact of a cancer diagnosis on their families,” said Richard L. Schilsky, MD, ASCO’s chief medical officer.

“It’s clear that high treatment costs are taking a serious toll not only on patients, but also on the people who care for them. If a family member has been diagnosed with cancer, the sole focus should be helping them get well. Instead, Americans are worrying about affording treatment, and, in many cases, they’re making serious personal sacrifices to help pay for their loved ones’ care.”

Photo by Junior Libby

A recent survey suggests Americans are nearly as worried about the cost of a cancer diagnosis as they are about dying from cancer.

The cost of cancer care was a top concern even among people who had no prior experience with cancer.

At the same time, cancer patients/survivors admitted to delaying or forgoing care due to costs, and caregivers reported taking “dramatic” actions to pay for their loved one’s care.

These are findings from the American Society of Clinical Oncology (ASCO)’s second annual National Cancer Opinion Survey.

The survey was conducted online by The Harris Poll from July 10, 2018, to August 10, 2018. It included 4,887 U.S. adults age 18 and older—1,001 of whom have or had cancer.

Cost among top concerns

Death and pain/suffering were the top concerns related to a cancer diagnosis. Fifty-four percent of respondents said death would be one of their greatest concerns if they were diagnosed with cancer, and the same percentage rated pain/suffering a top concern.

Forty-four percent of respondents said paying for cancer treatment would be a top concern, and 45% said the same about the financial impact of a cancer diagnosis on their family. When combined, financial issues were a top concern for 57% of respondents.

Paying for treatment was a top concern for:

• 36% of respondents who had/have cancer
• 51% of caregivers
• 43% of people with no prior cancer experience.

The financial impact on family was a top concern for:

• 39% of respondents who had/have cancer
• 55% of caregivers
• 42% of people with no prior cancer experience.

Cutting costs

Sixty-one percent of caregivers surveyed said they or another relative have taken a “dramatic” step to help pay for their loved one’s care, including:

• Dipping into savings accounts (35%)
• Working extra hours (23%)
• Taking an early withdrawal from a retirement account or college fund (14%)
• Postponing retirement (14%)
• Taking out a second mortgage or other type of loan (13%)
• Taking an additional job (13%)
• Selling family heirlooms (9%).

Twenty percent of cancer patients/survivors said they have taken actions to reduce treatment costs, including:

• Delaying scans (7%)
• Skipping or delaying appointments (7%)
• Skipping doses of prescribed treatment (6%)
• Postponing or not filling prescriptions (5%)
• Refusing treatment (3%).

“Patients are right to be concerned about the financial impact of a cancer diagnosis on their families,” said Richard L. Schilsky, MD, ASCO’s chief medical officer.

“It’s clear that high treatment costs are taking a serious toll not only on patients, but also on the people who care for them. If a family member has been diagnosed with cancer, the sole focus should be helping them get well. Instead, Americans are worrying about affording treatment, and, in many cases, they’re making serious personal sacrifices to help pay for their loved ones’ care.”

Photo by Junior Libby

A recent survey suggests Americans are nearly as worried about the cost of a cancer diagnosis as they are about dying from cancer.

The cost of cancer care was a top concern even among people who had no prior experience with cancer.

At the same time, cancer patients/survivors admitted to delaying or forgoing care due to costs, and caregivers reported taking “dramatic” actions to pay for their loved one’s care.

These are findings from the American Society of Clinical Oncology (ASCO)’s second annual National Cancer Opinion Survey.

The survey was conducted online by The Harris Poll from July 10, 2018, to August 10, 2018. It included 4,887 U.S. adults age 18 and older—1,001 of whom have or had cancer.

Cost among top concerns

Death and pain/suffering were the top concerns related to a cancer diagnosis. Fifty-four percent of respondents said death would be one of their greatest concerns if they were diagnosed with cancer, and the same percentage rated pain/suffering a top concern.

Forty-four percent of respondents said paying for cancer treatment would be a top concern, and 45% said the same about the financial impact of a cancer diagnosis on their family. When combined, financial issues were a top concern for 57% of respondents.

Paying for treatment was a top concern for:

• 36% of respondents who had/have cancer
• 51% of caregivers
• 43% of people with no prior cancer experience.

The financial impact on family was a top concern for:

• 39% of respondents who had/have cancer
• 55% of caregivers
• 42% of people with no prior cancer experience.

Cutting costs

Sixty-one percent of caregivers surveyed said they or another relative have taken a “dramatic” step to help pay for their loved one’s care, including:

• Dipping into savings accounts (35%)
• Working extra hours (23%)
• Taking an early withdrawal from a retirement account or college fund (14%)
• Postponing retirement (14%)
• Taking out a second mortgage or other type of loan (13%)
• Taking an additional job (13%)
• Selling family heirlooms (9%).

Twenty percent of cancer patients/survivors said they have taken actions to reduce treatment costs, including:

• Delaying scans (7%)
• Skipping or delaying appointments (7%)
• Skipping doses of prescribed treatment (6%)
• Postponing or not filling prescriptions (5%)
• Refusing treatment (3%).

“Patients are right to be concerned about the financial impact of a cancer diagnosis on their families,” said Richard L. Schilsky, MD, ASCO’s chief medical officer.

“It’s clear that high treatment costs are taking a serious toll not only on patients, but also on the people who care for them. If a family member has been diagnosed with cancer, the sole focus should be helping them get well. Instead, Americans are worrying about affording treatment, and, in many cases, they’re making serious personal sacrifices to help pay for their loved ones’ care.”