Patterns Of Post-Transplant Relapse And Progression Vary Among Multiple Myeloma Patients
A group of Spanish researchers published a summary last year of the patterns of relapse and progression they observed in multiple myeloma patients who underwent stem cell transplantation as part of their upfront therapy.
The researchers observed relapse in over half of the patients included in the study. Among these patients, the majority had only achieved a partial response after transplantation.
They also found that how a patient relapsed had an impact on their prognosis after relapse. Patients who relapsed based solely on changes in disease markers, such as their M-spike level, typically survived longer than patients whose relapse was marked by one of the typical symptoms of myeloma, such as increased calcium levels in the blood, kidney failure, anemia, or bone involvement.
Interestingly, the researchers found that the symptoms patients experienced at relapse were often very similar to those that they had at the time of diagnosis.
The investigators recommend that patients who have myeloma symptoms at the time of relapse be treated immediately.
However, for patients who relapse without any of the typical myeloma-related symptoms, the timing of re-treatment is less clear. The researchers recommend using increasing monoclonal (M) protein level as a indicator for early treatment.
The researchers also note that early detection of progression remains a challenge. They explain that attempts have been made to use biomarkers to detect early relapse. However, according to the Spanish researchers, it is not clear yet if these tools provide a clinical benefit.
Autologous stem cell transplantation is commonly used in the treatment of multiple myeloma.
In this procedure, a patient’s stem cells are harvested prior to high-dose chemotherapy. The stem cells are then re-infused into the patient after chemotherapy to replace the healthy bone marrow cells that were destroyed during the chemotherapy.
Previous studies have shown that patients who achieve a complete response after transplantation tend to have longer progression-free survival and overall survival compared to those who achieve only a partial response.
However, the authors of the current study note that all patients, even those who achieve a complete response, are at high risk of relapse over time.
The Spanish researchers point out that there is currently little data available on the patterns of relapse. What research there is indicates that such patterns are very heterogeneous.
The researchers therefore sought to investigate the characteristics of multiple myeloma patients at relapse following an autologous stem cell transplant that was given as part of the patient's initial treatment.
Specifically, the investigators assessed the presence and type of myeloma symptoms at the time of relapse. They defined asymptomatic relapse as relapse based on changes in biochemical markers of myeloma, such as high M-protein levels or an abnormal free-light chain ratio, in the absence of the typical myeloma symptoms.
Investigators from the university hospital in Barcelona, Spain, retrospectively assessed data from 170 multiple myeloma patients who had received an autologous stem cell transplant as part of their initial treatment at their institution between March 1994 and December 2011.
The median patient age was 56 years.
Two-thirds of the patients (67 percent) received conventional chemotherapy as their induction therapy; the remaining patients received regimens that included novel agents, such as thalidomide (Thalomid), Velcade (bortezomib), and Revlimid (lenalidomide).
Following transplantation, 73 patients received maintenance therapy with either interferon alpha-2b (77 percent), thalidomide alone (12 percent), or thalidomide plus Velcade (11 percent).
The median follow-up time was 3.9 years.
The researchers found that 48 percent of the patients achieved a complete response after transplantation.
Overall, 55 percent of the patients had relapsed or progressed as of December 2011. The majority of the patients (60 percent) who relapsed or progressed had only achieved a partial response after transplantation, while the remaining 40 percent relapsed or progressed from a complete response.
Half of the patients had symptoms of myeloma at the time of relapse, while the other half had no symptoms.
The investigators note that asymptomatic relapse was less common before 2000 than in the most recent decade (26 percent versus 55 percent, respectively). They explain that the difference may be due to the development of more effective drugs and therapies in recent years.
More patients with symptomatic relapse had an above-median bone marrow plasma cell percentage rate (67 percent versus 38 percent), anemia (49 percent versus 26 percent), and advanced myeloma (34 percent versus 7 percent) at diagnosis, compared to patients with asymptomatic relapse.
The median bone marrow plasma cell percentage at diagnosis was 43 percent, and advanced myeloma was defined in the study as Stage 3 myeloma according to the International Staging System.
Additionally, according to the Spanish researchers, the symptoms at relapse were similar to those at the time of diagnosis. For example, of the patients who had kidney failure at relapse, 55 percent had kidney impairment at diagnosis. Similarly, 59 percent of patients with extramedullary disease at relapse had extramedullary disease at diagnosis.
Extramedullary disease occurs when myeloma cells form tumors outside of the bone marrow, in the soft tissues or organs of the body. Previous research has shown that myeloma patients with extramedullary disease have a poorer prognosis than those without (see related Beacon news).
Reasons For Treatment At Relapse & Treatment Outcomes
The main reasons patients started treatment after relapse or progression were anemia (43 percent), new bone lesions (36 percent), extramedullary disease (24 percent), bone pain (14 percent), kidney failure (12 percent), and high calcium levels (9 percent).
The most common salvage (post-relapse) therapies were regimens based on Velcade (41 percent), followed by thalidomide (10 percent) and Revlimid (10 percent).
The overall response rate to salvage therapy was 45 percent, with 3 percent of patients achieving a complete response, 16 percent a very good partial response, and 26 percent a partial response.
More patients with asymptomatic relapse achieved at least a minimal response to salvage therapy than patients with symptomatic relapse (69 percent versus 44 percent).
Following stem cell transplantation, the median progression-free survival was 3.3 years and the median overall survival was 6.8 years.
Patients with asymptomatic relapse had a significantly longer overall survival (7.1 years) than those with symptomatic relapse (3.6 years).
The median overall survival after salvage therapy was 2.5 years.
When the researchers controlled for a number of different factors that could affect a patient's survival after relapse, they found that the only factors with a statistically significant impact on survival were: time to relapse, type of relapse (asymptomatic versus symptomatic), and the use of a second transplant as part of salvage therapy.
Patients who underwent a second transplant as part of their salvage therapy typically survived longer than those who did not. The authors of the study note, however, that this may be the result of other factors that they were not able to control for statistically. For example, patients who underwent a second transplant may have been in better overall health than those who did not.
For more information, please refer to in the journal Bone Marrow Transplantation (abstract).
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- Continued Response After Stem Cell Transplantation For Myeloma May Signal Improved Survival
- "Chemo Brain" May Affect Half Of Myeloma Patients After Initial Therapy, And Is Worsened By Stem Cell Transplantation