Gradual Response Better then Fast Response in Myeloma Therapy?

Share Button

“The five-year survival rate was 77 percent for (myeloma) patients who achieved their best response to initial treat­ment in more than 120 days, and 56 percent for patients who achieved their best response in 120 days or less.”

According to the studies discussed and excerpted below, the newly diagnosed myeloma patient who responds gradually to his/her therapy can live up to 21% longer than the MMer who responds faster. The study doesn’t say that the MMer must achieve MDR or even complete remission. The study just cites patients who achieve their “best response.” A deep response to treatment is a strong but not perfect predictor of overall survival.

According to the American Cancer Society, the average five year survival of MMers is about five years.

Unfortunately, while the study says that gradually responding is good, it doesn’t say how MMers can respond gradually to their initial therapy. Some newly diagnosed MMers respond rapidly and some don’t…

Patients who achieved their “best response” more gradually live longer, on average, than MMers who respond quickly- in less than 120 days.  The study doesn’t say what is meant by a “best response.” According to the study, undergoing an autologous stem cell transplant or not makes no difference in how long an MMer lives. What matters is how gradual he or she responds to treatment.

What does the study confirm?

  1. Average five-year survival can improve by more than 20% for those responding gradually to therapy
  2. Deep response to treatment does not guarantee long overall survival
  3. “Complete response” to initial treatment does not guarantee long overall survival either

If a newly diagnosed MM patient acheived their “best response” to chemotherapy, is it possible that evidence-based complementary therapies such as nutrition, supplementation, lifestyle, etc. can lengthen the MMers remission? I think it is.

Thank you,

David Emerson

  • MM Survivor
  • MM Cancer Coach
  • Director PeopleBeatingCancer

Recommended Reading:

Multiple Myeloma Patients are ALL “Toxicity-Vulnerable”

Multiple Myeloma IT Response Alphabet Soup- MRD, sCR, CR, VGPR, PR…

Multiple Myeloma Specialists- MM Cancer Coaching


Gradual Response To Initial Treatment May Be Sign Of Better Prognosis In Multiple Myeloma

“Results of a retrospective study conducted at the Mayo Clinic indicate that multiple myeloma patients who respond more gradually to their initial treat­ment may have better overall survival.

Specifically, the authors of the new study find that newly diag­nosed patients who required more than 120 days to achieve their best response to initial treat­ment had better progression-free and overall survival than patients who achieved their best response in 120 days or less.

The five-year survival rate was 77 percent for patients who achieved their best response to initial treat­ment in more than 120 days, and 56 percent for patients who achieved their best response in 120 days or less.

The positive impact on survival of a more gradual response to treatment was seen both in patients who re­ceived a stem cell trans­plant as part of their initial treatment and in patients who did not.

The impact also was present when the researchers controlled for a variety of other factors that could affect prognosis, such as the patient’s age, their best response to treatment, and whether or not they had high-risk chromosomal abnormalities.

The study is based on data for more than 1,000 multiple myeloma patients who were diagnosed between 2005 and 2015 at the Mayo Clinic in Rochester, Minnesota.

Based on their findings, the study authors suggest that patients who respond more gradually to initial treat­ment may represent a subgroup of patients whose disease is less likely to progress rapidly and less likely to develop resistance to treat­ment.

Background

Overall survival in multiple myeloma patients has increased markedly since the introduction of novel therapies such as thalidomide, Revlimid (lenalidomide), and Velcade (bortezomib) in the last 20 years (see related Beacon news article).

The new treatments have given physicians more options with which to treat multiple myeloma, extending the time each patient has until treatment options are exhausted.

In addition, the new treatments have made it possible to achieve deeper responses to treatment, which generally lengthens the time until a patient’s disease progresses and a new treatment must be tried.

Yet a deep response to initial treatment does not always guarantee long overall survival. The authors of the new study note that “survival analyses in both transplant and non-transplant populations have demonstrated that up to 20 percent of patients achieving a [complete response to initial treatment] will die within four years.”

Researchers therefore are trying to identify additional factors to better predict survival in myeloma patients. Knowledge of such factors could make it easier for doctors to customize therapy based on a patient’s prognosis.

Extensive research has demonstrated that both the duration of a patient’s initial response to treatment, and their depth of response, are strong (but not perfect) predictors of patient survival.

There has been conflicting evidence, however, about whether the speed of a patient’s response to initial treatment positively or negatively affects patient prognosis.

Studies done before the introduction of novel myeloma therapies suggested that a rapid response to initial treatment was associated with poorer survival outcomes. Studies involving patients who have received treatment with novel myeloma therapies have had more mixed results. For example:

  • Relapsed patients who received treatment with Velcade-based regimens in a clinical trial had longer time to progression if their M-spike decreased fast after the start of treatment (reference)
  • Newly diagnosed patients in a combined analysis of results from three European clinical trials had survival outcomes that were unaffected by whether or not the patients achieved a complete response before or after six months (reference)
  • Newly diagnosed patients in a single center U.S. clinical trial had lower overall survival if their serum free light chain level dropped rapidly after the start of treatment (reference)
  • Relapsed patients in an international trial testing the efficacy of a Ninlaro (ixazomib)-based regimen had longer progression free survival when they took longer to achieve their best response to treatment (reference)

Given the lack of consensus in studies investigating speed of response in the age of novel therapies, the authors of the new study decided to investigate the issue using data from patients at their own institution.

Study Design

The study authors retrospectively analyzed data from all 1,099 multiple myeloma patients who were diagnosed at the Mayo Clinic’s Rochester, Minnesota location between 2005 and 2015, received initial treatment with novel agents, and achieved at least a very good partial response to initial treatment.

The median patient age at diagnosis was 63 years old.

The most common initial treatments the patients received included:

  • Revlimid and dexamethasone (33 percent of patients),
  • Velcade, cyclophosphamide, and dexamethasone (24 percent), and
  • Velcade, Revlimid, and dexamethasone (16 percent).

One third of the patients received a stem cell transplant as part of their initial treatment, which was defined as receiving a transplant within 12 months of starting initial treatment.

The median follow-up time was 3.8 years. The median length of initial therapy across all patients in the sample was 1.8 years, the authors told The Beacon. First-line therapy varied in length across patients depending, for example, on whether patients had an upfront transplant and whether they underwent maintenance therapy.

The median overall survival from initial diagnosis was 8.8 years.

Study Results

The study authors found that median time to best response among the patients in their dataset was 4.9 months, and the median duration of best response was 1.8 years.

More importantly, the researchers found that the time it took for patients to achieve their best response to initial treatment affected both their progression-free survival and overall survival.

The researchers divided the patients in the study into two groups:

  1. Patients who achieved their best response to treatment in 120 days or less
  2. Patients who took more than 120 days to reach their best response.

Median progression-free survival was 2.1 years for patients in the first (fast-responding) group, and 3.3 years in the second (slow-responding) group.

Median overall survival was about six years in the first (fast-responding) group, and has not yet been reached in the second (slow-responding) group.

The five-year survival rates are 56 percent and 77 percent for the fast- and slow-responding groups, respectively.

These differences in survival between the two patient groups are statistically very significant.

Just as importantly, the differences were found to persist even when the authors controlled for other factors that could affect a patient’s prognosis.

For example, the researchers divided patients into two different age groups, with 65 years of age as the dividing line. In both age groups, time to best response still had a significant impact on survival. Patients who reached their best response in longer than 120 days had longer progression-free survival and overall survival than patients in the same age group who had more rapid responses to treatment.

The researchers got the same result when they divided patients into two groups based on whether or not they had an upfront transplant as part of their initial therapy. Once again, the patients in both these groups who took more than 120 days to reach their best response had the better survival outcomes.

The study authors also estimated several different statistical models to test further whether other factors, such as gender, best response to initial treatment, type of initial treatment, size of initial M-spike, stage at diagnosis, or presence of high-risk chromosomal abnormalities could explain away the impact of time to best response.

In all models, however, time to best response was still a significant factor.

Given these results, the authors write that “it is possible that multiple myeloma responding more gradually to initial treatment portends some biologic advantage that is independent of, and not simply a surrogate for,” a patient’s disease stage or chromosomal abnormalities. Myeloma patients who respond more gradually to treatment, the authors continue, may be “less prone to developing treatment resistance and subsequent disease progression.”

Time to plateau as a predictor of survival in newly diagnosed multiple myeloma

“Response rates in newly diagnosed multiple myeloma have improved dramatically with the introduction of highly effective novel therapies. However, survival in patients achieving optimal responses to initial treatment can vary significantly, and new prognostic indicators are required to improve risk stratification…

 

 

Leave a Comment:

5 comments
Add Your Reply