During the second day of the American Society of Clinical Oncology (ASCO) annual meeting in Chicago last month, Dr. Amrita Krishnan from the City of Hope National Medical Center in Duarte, California, gave a presentation on the current status of stem cell transplantation in the treatment of multiple myeloma.

Dr. Krishnan started her presentation by saying that in the United States, multiple myeloma patients make up the largest group of cancer patients undergoing stem cell transplantation.

An autologous (own) stem cell transplant is a procedure in which stem cells are harvested from a patient prior to high-dose chemotherapy and later re-infused into the patient’s body to replace the cells that were destroyed during the chemotherapy.

Autologous transplants are the most common kind carried out with myeloma patients, and are the type of transplant implied in general discussions of transplants and myeloma.

Early clinical trials showed that high-dose chemotherapy followed by stem cell transplantation significantly improved survival outcomes in myeloma patients.

However, during her presentation, Dr. Krishnan pointed out that these trials were performed before novel agents for myeloma treatment, such as Revlimid ^[1] (lenalidomide), thalidomide ^[2] (Thalomid), and Velcade ^[3], became available. In the past decade, the introduction of these treatments has led to further improvement in survival.

In her presentation, Dr. Krishnan addressed the question of how to incorporate treatment with these novel agents into a regimen involving stem cell transplantation. Specifically, she focused on the questions of when to perform a transplant, how to determine transplant eligibility, and what type of transplant and post-transplant therapy is best suited for particular groups of patients.

According to Dr. Krishnan, there is currently no consensus on how many cycles of initial therapy, also called induction therapy, a patient should undergo prior to receiving high-dose chemotherapy and a stem cell transplant. She pointed out that four cycles of induction therapy are currently standard and result in minimal side effects and high response rates.

However, Dr. Krishnan mentioned a trial in which 75 percent of relapsed patients receiving induction therapy with Revlimid, Velcade, and dexamethasone ^[4] (Decadron) had better responses after six or eight cycles of induction therapy. Results from earlier clinical trials suggest that a deeper response prior to a transplant may translate into improved progression-free survival post transplant.

Dr. Krishnan cited a Spanish study conducted before the introduction of novel agents.  Results of this trial showed that “patients who achieved a complete response had better event-free and overall survival compared to patients who were in partial response prior to transplant,” said Dr. Krishnan.  “This was not statistically significant yet, but there was a trend toward that.”

According to Dr. Krishan, there is also insufficient data regarding whether a patient should receive a transplant after one round of induction therapy or wait until after relapsing and receiving a second round of induction therapy.

She pointed out that a clinical trial is currently being conducted to compare early and delayed transplants in newly diagnosed patients receiving induction therapy with Revlimid, Velcade, and dexamethasone.

The second question that Dr. Krishnan addressed was how to determine transplant eligibility. She pointed out that the median age of a myeloma patient is about 70, but that stem cell transplants are typically reserved for patients 65 years and younger.

However, she explained, "A transplant can be considered in the older patient. Mortality can be managed with the appropriate reduction in melphalan dosing.”

Recent research has shown that age should not be the sole determining factor for transplantation eligibility.

“Age alone is not an absolute indicator [for stem cell transplantation],” explained Dr. Krishnan.

Factors such as organ function, unrelated disease, and a geriatric assessment should be taken into account when deciding whether or not a patient is suitable for a transplant.

“In older patients, we should consider frailty, things such as weakness, endurance, gait speed, weight loss, and comorbidities," added Dr. Krishnan.

Lastly, Dr. Krishnan discussed the issue of treating patients with high-risk disease.

Myeloma patients with high-risk chromosomal abnormalities -- including translocation t(4,14), translocation t(14,16), deletion 13, or deletion 17p -- typically have low response rates to available induction regimens and require a different approach to treatment.

Research has demonstrated that a Velcade-based initial therapy particularly benefits patients with the translocation t(4,14), but is insufficient for patients with the 17p deletion.

However, one trial showed that 17p deletion patients who were treated with Velcade during both the initial treatment and the maintenance period had better progression-free and overall survival than patients treated with vincristine ^[5], doxorubicin ^[6] (Adriamycin), and dexamethasone (abbreviated VAD).

"It suggests that it's not just induction [initial therapy], but length of exposure to bortezomib [Velcade] that may be important," said Dr. Krishnan.

According to Dr. Krishnan, donor (allogeneic) stem cell transplantation may also be considered for patients with high-risk myeloma. However, Dr. Krishnan pointed out that this procedure is controversial, and that clinical trials have shown conflicting results regarding the potential benefit of receiving a donor transplant versus an autologous transplant.

Dr. Krishnan mentioned that there is currently no standard approach to post-transplant therapy. Options include one or more of the following: no therapy, a second transplant, maintenance therapy, or consolidation therapy,  which is additional (usually intensive) therapy for a predefined period of time.

An ongoing trial is comparing the benefits of consolidation therapy versus a second transplant or maintenance therapy.

For more information, please see the article ^[7] (pdf) Dr. Krishnan wrote to accompany her presentation.