Sustained Complete Response To Initial Treatment Associated With Substantial Survival Benefit In Multiple Myeloma

In a retrospective study of over 350 multiple myeloma patients who had a complete response to their initial line of therapy, researchers in the United States have found that a longer duration of response is associated with substantially longer overall survival.
In addition, the study authors found that patients who started second-line treatment due to a biochemical relapse had longer overall survival than those who started second-line treatment due to a symptomatic relapse.
A symptomatic relapse is one in which the patient experiences new bone lesions, anemia, or other defining symptoms of multiple myeloma. A biochemical relapse, in contrast, is one where there are no new symptoms of the disease, but the patient's M-spike or serum free light chain levels increase by a substantial amount.
Patients in the study who sustained a complete response for 24 months or longer after the start of their initial treatment had median overall survival of 150 months (12.5 years) compared to 81 months (6.75 years) for patients who kept their complete response for less than 24 months.
The difference in overall survival between the two groups of patients remained statistically significant even when the researchers controlled for the potential influence of patient age, whether the patients had received a stem cell transplant or not as part of their initial therapy, and whether they had received maintenance therapy.
The difference in overall survival between the two groups was not simply the result of the one group staying in remission longer than the other. Length of remission also was associated with longer overall survival when it was measured from the time of disease progression, rather than from the start of treatment after initial diagnosis.
Overall survival from the time of relapse was 89 months (7.4 years) for patients who kept their complete response for 24 months or longer, versus 56 months (4.7 years) for patients who kept their complete response for less than 24 months.
The type of relapse a patient experienced also was associated with differences in overall survival. Patients in the study who started second-line treatment due to biochemical relapse had longer overall survival (125 months, or 10.4 years) than patients who started second-line treatment because of symptomatic relapse (81 months, or 6.75 years).
The researchers speculate that differences in disease biology across patients in their sample are likely to account for many of the survival differences they observed. Patients with more aggressive disease, for example, are likely to have both shorter durations of response and shorter overall survival. Aggressive disease also may be more likely to lead to symptomatic rather than biochemical relapse, leading to an association between symptomatic relapse and shorter overall survival.
The study authors also speculate, however, that treatment before the onset of new symptoms may improve survival by preventing organ damage that can hamper patient health and limit future treatment options.
Background Information
Previous research has shown that achieving a deep response to initial treatment is associated with improved overall survival (see, for example, the study results summarized in this Beacon news article).
Previous research also has indicated that sustained deep responses are associated with better survival than short responses. However, according to the authors of the new study, these findings have been mainly in studies involving patients who had a stem cell transplant as part of their initial therapy.
In the current study, the researchers sought to assess the the impact of duration of response in patients who achieved a complete response during initial therapy, regardless of whether or not a patient had a stem cell transplant as part of their initial treatment. The authors also sought to investigate what sort of relapses occur when patients come out of remission, and whether the type of relapse affects a patient's survival prognosis.
Study Design
The new study was conducted by researchers at the Mayo Clinic. The study authors retrospectively analyzed data from 351 multiple myeloma patients who were seen at their institution between July 2004 and January 2016 and had achieved a complete response to their first-line treatment.
The median patient age at the time of diagnosis was 61 years old. About one fifth of patients (21 percent) had high-risk chromosomal abnormalities, defined as t(4;14), t(14;16), t(14;20), del(17p), and monosomy 17.
All but three patients received induction therapy with novel agents. Three quarters of the patients received an autologous (own) stem cell transplant, and 39 percent received maintenance therapy as part of their first-line therapy. Maintenance therapy was mostly Revlimid- or Velcade-based (57 percent and 36 percent, respectively).
Study Results
Across all patients in the study, the median time to achieving a complete response was eight months.
The median duration of complete response was 24 months. Overall, 9 percent of the patients stayed in complete remission for less than 6 months, 12 percent for 6 to 12 months, 14 percent for 12 to 18 months, 14 percent for 18 to 24 months, and 51 percent stayed in complete remission for 24 months or longer.
At the time of last follow-up, 68 percent of patients had relapsed / progressed.
Type Of Relapse / Progression
The researchers established four categories of relapse / progression:
- Symptomatic relapse – Progression with lytic lesions, anemia, a plasmacytoma, or other symptoms of myeloma-related end-organ damage
- Biochemical relapse / progression – A 25 percent or more increase in M-spike with at least a 0.5 g/dL increase
- Biochemical loss of complete response with re-emergence of a monoclonal protein – Two consecutive positive immunofixation values in serum / urine, or rise in M-spike not meeting the criteria for biochemical or symptomatic progression
- Biochemical loss of complete response with abnormal free light chain ratio only – Two consecutive abnormal free light chain ratios in patients with light chain myeloma who do not meet criterion (3) for relapse / progression
Of the patients who had relapsed, 25 percent experienced a symptomatic relapse, 24 percent a biochemical relapse, 37 percent had a positive urine/serum immunofixation or a rise in M-spike, and 14 percent had a loss of complete response with an abnormal free light chain ratio.
Characteristics Of Patients With Long And Short Durations Of Response
When the researchers compared the characteristics of patients who sustained their complete response for 24 months or longer after their initial treatment with the characteristics of patients who kept their complete response for less than 24 months, they found no difference in age, gender, bone marrow plasma cell percentage at diagnosis, share of patients with high-risk chromosomal abnormalities, or share of patients who received a stem cell transplant as part of their first-line treatment.
However, patients who sustained their complete response for 24 months or longer after their initial treatment were less likely to have advanced disease (ISS Stage 3) than patients who kept their complete response for less than 24 months (22 percent with ISS Stage 3 disease versus 37 percent, respectively).
In addition, patients who sustained their complete response for 24 months or longer were more likely to have received maintenance therapy than patients who kept their complete response for less than 24 months (42 percent versus 31 percent, respectively).
Overall Survival
After a median follow-up time of 72 months from the start of therapy, the median overall survival for all patients was 123 months (10.25 years).
Patients who sustained their complete response for 24 months or longer after their initial treatment had significantly longer overall survival (150 months / 12.5 years) than patients who kept their complete response for less than 24 months (81 months / 6.75 years).
The association between duration of response and overall survival was lessened somewhat when the researchers controlled for patient age, disease stage at diagnosis, and whether or not the patient had a stem cell transplant or maintenance therapy. The association, however, was still large and statistically significant.
There also was an association between duration of initial complete response and a patient's survival from time of relapse. Overall survival was 89 months (7.4 years) from the time of relapse for patients who kept their complete for 24 months or longer, compared to 56 months (4.7 years) for patients who kept their complete response for less than 24 months.
When the researchers looked at patients who started second-line treatment because of biochemical or symptomatic progression, they found that overall survival from the start of first-line treatment was longer for patients who started second-line treatment for biochemical progression (125 months / 10.4 years) compared to those who started second-line treatment for symptomatic progression (81 months / 6.75 years).
For more information, please see the study by Sidana, S. et al., “Relapse after complete response in newly diagnosed multiple myeloma: implications of duration of response and patterns of relapse,” in Leukemia, October 15, 2018 (abstract).
Related Articles:
- Revlimid, Velcade, and Dexamethasone, Followed By Stem Cell Transplantation, Yields Deep Responses And Considerable Overall Survival In Newly Diagnosed Multiple Myeloma
- Eyelid-Related Complications Of Velcade Therapy: New Insights And Recommendations
- Nelfinavir-Velcade Combination Very Active In Advanced, Velcade-Resistant Multiple Myeloma
- Nelfinavir Shows Only Limited Success In Overcoming Revlimid Resistance In Multiple Myeloma Patients
- Early Use Of Radiation Therapy Associated With Shorter Survival In Multiple Myeloma
Wow. It's great we are getting results of these analyses. Thank you heaps from New Zealand