In a recent study published in the journal Blood, researchers reviewed pre­vi­ously reported research and found a general correlation between “complete response” to ther­apy and survival for multiple myeloma patients.

Complete response, which is defined as a normal bone marrow evaluation and a negative immuno­fix­a­tion (a test to detect ab­nor­mal anti­bodies in the blood or urine), has been correlated to patient out­come for many blood cancers. However, conventional chemotherapy has rarely produced com­plete responses in myeloma patients.

The sig­nif­i­cance of a com­plete response to myeloma treat­ment was not important until the introduction of high dose ther­apy and autologous stem cell trans­plants ^[1], in which the patient’s own bone marrow or stems cells are used.

In their review, the study authors found that among myeloma patients who received an au­tol­o­gous stem cell trans­plant, achieving com­plete response or near com­plete response, known as “very good partial remission,” was correlated with pro­gres­sion-free survival and usually longer over­all survival. A very good partial remission is possible with a positive immuno­fix­a­tion but a normal electrophoresis.

The rates of com­plete response and very good partial remission in myeloma patients increased rapidly with newer treat­ment ther­a­pies that in­clude thalidomide ^[2] (Thalomid), Velcade ^[3] (bor­tez­o­mib), and Revlimid ^[4] (lena­lido­mide).

In patients taking Velcade or Revlimid in addi­tion to dexamethasone ^[5] (Decadron), increased response rates have led to sig­nif­i­cantly longer time to next ther­apy and pro­gres­sion-free survival. Additionally, the com­bi­na­tion of Revlimid and dexa­meth­a­sone has been shown to extend over­all survival compared to dexa­meth­a­sone alone.

In newly diag­nosed patients, the authors noted that a com­bi­na­tion of melphalan ^[6] (Alkeran), prednisone ^[7], and thalido­mide yielded higher response rates and longer pro­gres­sion-free survival than mel­phalan and pred­ni­sone alone. For the com­bi­na­tion of Velcade, mel­phalan, and pred­ni­sone, one study has shown the com­plete response rate to be 30 per­cent, which is com­parable to the com­plete response rate for high dose ther­apy. These patients had longer pro­gres­sion-free survival than patients receiving mel­phalan and pred­ni­sone alone. However, extended over­all survival has not yet been shown.

Although the authors show that com­plete responses are correlated with increased survival, they also show that there are many addi­tional factors that affect the impact com­plete response has on survival.

For instance, among patients that had a com­plete response to Velcade, mel­phalan, and pred­ni­sone, the median com­plete response duration was 24 months. However, among patients that had a com­plete response to mel­phalan and pred­ni­sone alone, the median was only 12.8 months. The authors suggest that the quality of the com­plete response to the Velcade regi­men was probably better.

In a trial com­par­ing single and double au­tol­o­gous stem cell trans­plants, com­plete response and very good partial remission rates were similar based on patients who intended to undergo ther­apy. However, event-free survival and over­all survival were sig­nif­i­cantly longer for the double trans­plant group, indicating a deeper response. Among patients who actually underwent trans­plan­ta­tion, response rates were sig­nif­i­cantly higher among patients receiving a double trans­plant.

The impact of com­plete response also varies with age. In elderly patients with multiple myeloma, treat­ment can increase the odds of com­plete response without actually extending pro­gres­sion-free survival. The authors suggest that in elderly and frail patients, com­plete response might not be the objective of treat­ment, particularly for more aggressive treat­ments that may produce more frequent or more severe toxicities.

Additionally, according to one study, patients who pre­vi­ously had mono­clonal gam­mop­athy of undetermined sig­nif­i­cance (a blood disorder that can progress to myeloma) or smol­der­ing multiple myeloma (myeloma that does not show symp­toms) may have extended survival without attaining com­plete response. In another study, patients with stage 1, or non-aggressive, myeloma did not show any survival benefit from achieving better responses. However, studies have shown that patients with poor prognosis, or aggressive myeloma, show sig­nif­i­cant survival benefit from attaining com­plete response or very good partial remission.

Despite the positive prognosis asso­ci­ated with a com­plete response, the end goal should not necessarily be to merely achieve com­plete response. Instead, the authors suggest that the goal should be to deepen and maintain response by reducing the tumor cell mass.

For more in­for­ma­tion, please see the study in the journal Blood ^[8](pdf).