Long-term Responses in Myeloma

Yes, younger, healthier newly diagnosed MM patients with less active MM sometimes have long-term responses in myeloma. Yes, aggressive treatment in the form of autologous stem cell transplantation can put a percentage of NDMM patients into deep remission. This is not news.

The study linked and excerpted below is commenting on long-term responders in MM who undergo aggressive treatment in the form of an autologous stem cell transplant (ASCT).

I am a long-term MM survivor. In my 25+ experience studying and writing about MM, conventional oncology continually focuses on the long-term responders and tries to figure out why and how to increase the small group of long-term responders (small as in 9%-14%).

If you are a newly diagnosed MM patient and you want to go-for-it, that’s great. It is your life. My problem is with the vast majority of NDMM patients who are not long-term responders. People who will live a crumby quality of life if prescribed the aggressive, highly toxic therapy plan that is the FDA Standard-of-care for all newly diagnosed MM patients.

If you are a NDMM patient, consider a low dose approach to your therapy plan. Consider what Vincent Rajkumar M.D. would call the control approach to the cure vs. control debate in MM.

While we’re on the subject of managing the NDMM patient’s MM, consider evidence-based non-conventional therapies such as:

Nutrition
Supplementation and
Lifestyle Therapies

Experience has shown me that combining the best of conventional and non-conventional therapies in MM is the most effective way to enhance both quality-of-life and quantity-of-life.

It is important to point out the conventional MM oncology can and does achieve long-term responses in myeloma. The key is to figure out your goals, your priorities and make those clear to your oncologist.

If you would like to learn more about both conventional and non-conventional MM therapies send me an email at David.PeopleBeatingCancer@gmail.com

Good luck,

David Emerson

MM Survivor
MM Cancer Coach
Director PeopleBeatingCancer

Multiple myeloma patients with a long remission after autologous hematopoietic stem cell transplantation

“Abstract-

Autologous stem cell transplantation (autoHCT) is considered standard of care for newly diagnosed multiple myeloma (MM). Although most patients eventually progress after autoHCT, a small proportion achieve a durable response. In this retrospective study we included 1576 patients, 244 (15%) of whom were long-term responders (LTR), defined as having a progression-free survival (PFS) of ≥8 years after transplant.

Patients in the LTR group were younger than the non-LTR group ,
less likely to have high-risk cytogenetics
more often had <50% bone marrow plasma cells
and R-ISS stage I disease

More patients in the LTR group received post-transplant maintenance (63% vs. 52%; p = 0.002).

Patients in the LTR group had higher rates of complete response (CR) at day100 (41% vs. 27%; p < 0.001) and at best post-transplant response (70% vs. 37%; p < 0.001), compared to the non-LTR group. Patients in the LTR groups had a median PFS of 169.3 months and the median overall survival (OS) had not been reached. The leading cause of death in the LTR was disease progression. In conclusion, 15% of patients in the cohort were LTR after upfront autoHCT, with distinct characteristics and a median PFS of more than 14 years.

Introduction

Advancements in anti-myeloma therapeutics have led to improved outcomes for patients with multiple myeloma (MM)…

However, most patients eventually progress [2, 3], and MM is generally considered an incurable disease. Interestingly, a small proportion of patients do achieve durable remission after autoHCT.

Terpos et al. described a cohort of 406 MM patients treated at a single center in Greece between 1994 and 2010, and found that 9% (n = 36) of newly diagnosed MM patients experienced a progression-free survival (PFS) of at least 7 years [4]. Only 29% of patients in that cohort underwent upfront autoHCT.

Few reports have focused on MM patients with prolonged remissions after autoHCT; most of which had small numbers of patients and used varying methodologies. A single-center analysis from Spain identified 54 (22%) of 250 patients who were transplanted between 1990 and 2015 as patients with prolonged remission following autoHCT, defined as achieving a sustained response for more than 5 years after autoHCT [5].

A report from the Mayo Clinic identified 46 (9%) of 509 patients as exceptional responders after autoHCT, defined as having a PFS of at least eight years without any maintenance therapy [6]….

Response definitions and MRD evaluation

We used the International Myeloma Working Group (IMWG) criteria to evaluate the response and progression [7]. Patients were categorized as having:

complete response (CR),
stringent CR (sCR),
very good partial response (VGPR),
partial response (PR),
stable disease (SD), or
progressive disease (PD).

MRD status was assessed using eight-color next-generation flow cytometry (NGF) with a sensitivity of 1/10^-5 cells (0.001%), based on acquisition and analysis of at least two million events.

Results

Patient, disease, and treatment characteristics

Our analysis included a total of 1576 NDMM patients who underwent autoHCT at our institution, and 224 (14%) were identified as LTR. Patients in the LTR group were somewhat younger than the non-LTR group (median age 58.4 vs. 59.5 years; p = 0.012), and were less likely to have high-risk cytogenetic abnormalities (4% vs. 14%; p < 0.001).

Patients in the LTR group more often had R-ISS stage I disease (43% vs. 34%) and less often had R-ISS stage III disease (3% vs. 10%) compared those in the non-LTR group (p = 0.010). Furthermore, patients in the LTR group more often had a low burden of disease in the bone marrow at diagnosis, defined as bone marrow plasma cells <50% (67% vs. 58%; p = 0.018)…

Responses and MRD outcomes

Patients in the LTR group more often achieved a hematological response of ≥VGPR prior to autoHCT (50% vs. 41%; p = 0.009), and more often had MRD negative status prior to autoHCT (52% vs. 35%; p = 0.016) compared to those in the non-LTR group. Of note, pre-transplant MRD status was missing in the majority of patients, 73% of the patients in the LTR group and 77% of the non-LTR group.

At day 100 post-transplant, a higher percentage of patients in the LTR group had a hematological response of ≥ CR compared to those in the non-LTR group (41% vs. 27%; p < 0.001). Similarly, at best post-transplant response evaluation, a higher percentage of patients in the LTR group had a hematological response of ≥CR compared to the non-LTR group (70% vs. 37%; p < 0.001)…

Survival outcomes

The median follow-up time for the entire cohort was 83.7 (range 0.2–262.0) months. As expected, patients in the LTR group had longer median follow-up compared to the non-LTR group [126.1 (range 96.0–254.9) months vs. 73.9 (range 0.2–262.0) months; p < 0.001]. Median follow-up among survivors was 127.3 (range 96.0–254.9) months in the LTR group and 99.3 (range 0.9–262.0) months in the non-LTR group (p < 0.001).

The most common cause of death among the LTR was progressive MM (35%), followed by second primary malignancies (22%) (Supplementary Table 1). In the non-LTR group, 159 (12%) patients developed a second primary malignancy, compared to 36 (15%) in the LTR group (p = 0.24)…

Discussion

Although MM is considered an incurable disease, in the present study we identified a distinct subset of patients, approximately 15% of the cohort, who had a median PFS of >14 years after induction therapy and autoHCT- long-term responses in myeloma.

These LTR were:

younger,
more likely to have R-ISS stage I disease,
standard-risk cytogenetics,
lower burden of disease in the bone marrow
and more often received post-transplant maintenance.

LTR also had better pre- and post-transplant responses, including higher rates of MRD negativity prior to autoHCT.

In conclusion, we identified a distinct subset of patients, approximately 15% of the cohort, who had a long median PFS of >14 years after induction therapy and autoHCT. These LTR were younger, more likely to have R-ISS stage I disease, standard-risk cytogenetics, and more often received post-transplant maintenance.”

Recently Diagnosed or Relapsed? Stop Looking For a Miracle Cure, and Use Evidence-Based Therapies To Enhance Your Treatment and Prolong Your Remission

Long-term Responses in Myeloma

David Emerson

Multiple myeloma patients with a long remission after autologous hematopoietic stem cell transplantation

Introduction

Response definitions and MRD evaluation

Results

Responses and MRD outcomes

Survival outcomes

Discussion

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