Physicians discussed upfront and induction therapy at the XII International Myeloma Workshop (IMW) last month. During their discussion, they focused on stem cell transplantation as an early treatment method for eligible multiple myeloma patients.

The concepts of upfront and induction therapy are very similar. Upfront therapy is any therapy given to previously untreated patients, while induction therapy is defined as the first treatment toward reducing the number of cancer cells in a patient before subsequent treatments. Therefore, this IMW discussion focused on the very first steps doctors take during treatment of multiple myeloma and the role of stem cell transplantation.

In the 1990s, doctors administered high doses of the chemotherapy drug melphalan to early-stage myeloma patients. This drug created a durable response without maintenance therapy and improved average patient life expectancy.

Newer treatment drugs like Velcade (bortezomib), thalidomide (Thalomid), and dexamethasone have since emerged. The array of effective drugs available today permits doctors to stop using such high doses of melphalan, yet also helps a growing number of patients achieve remission.

Once doctors bring the number of cancer cells down as much as possible with these treatments, they might follow up with high-dose therapy and stem cell transplantation. Sundar Jagannath, MD, noted that doctors who do transplants early and consistently have more patients with very good partial remission or complete remission.

Though the transplant method does not operate much differently than it did in 1990, views on the importance of an early transplant have changed as treatment methods have improved.

As survival time increases, Jagganath worries that patients may not place as much importance on an immediate stem cell transplant. Patients alive after three years might think that they can delay transplant until relapse even though they are not disease-free and still require more therapy.

Also, a study conducted by Jean-Paul Fermand, MD, provides evidence that the timing of a transplant does not matter in terms of survival. According to Jagannath, some people may use the study as a reason to delay transplantation.

Jagganath stated that his personal recommendation for intermediate induction therapy is a combination of treatment drugs, followed by stem cell transplant and a short period of maintenance therapy. He added that it is better to have a transplant upfront rather than in a relapse situation, citing that the median duration of remission with upfront transplantation is five to seven years, yet only one year in a relapse situation.

Though Sagar Lonial, MD, stated that there must be further research done on the effectiveness of stem cell transplantation in achieving remission, he also said it is key that “patients are referred to the transplant centers within the first four cycles of their induction therapy to have the discussion about transplant and have stem cells mobilized.”

He also said that patients who achieve complete remission with induction therapy have the opportunity to collect and store stem cells, in case a transplant is recommended in the future.

Both doctors agreed that even if patients do not want a transplant upfront, in the face of a relapse, they should have one instead of using a newer drug or melphalan. According to Jagganath, “Once you have multiple relapses, then high-dose melphalan will not give you much time.”

For more information, please refer to the IMW presentation transcript (pdf) provided by the MMRF.