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The case for longer treatment in MM: Part 1
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
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
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
The case for longer treatment in MM: Part 2
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
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
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.
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