Suggested update to current IMWG complete response criteria for MM

Response assessment in multiple myeloma (MM) is guided and classified based on the criteria set out by the International Myeloma Working Group (IMWG) in 2016.¹ With the current advances in MM therapies and the increasing number of patients achieving a complete response (CR), a uniform application of response criteria is paramount. According to the IMWG, CR is defined as negative serum and urine M-protein immunofixation (IF), along with the presence of < 5% plasma cells (PCs) in bone marrow (BM) biopsy.¹ The same guidelines state that in cases where only the BM fulfils the CR criteria, a second BM biopsy is recommended at the time of serum and urine IF negativity.

Recently, Tschautscher et al. challenged the need for a second BM biopsy to confirm CR in patients who will be undergoing autologous stem cell transplantation (ASCT).² The results of this retrospective study were published in Blood Cancer Journal and are discussed below, together with a summary of the current IMWG 2016 criteria.

IMWG 2016 response criteria & new suggestion

The current IMWG response criteria (2016) for MM¹ and the novel suggestion from Tschautscher et al.² are depicted in Figures 1 and 2, below.

Figure 1. IMWG (2016) response criteria for MM and new suggestion^1,2

ASCT, autologous stem cell transplantation; BM, bone marrow; CR, complete response; FLC, free light chain; IF, immunofixation; IHC, immunohistochemistry; IMWG, International Myeloma Working Group; PC, plasma cell; PR, partial response; sCR, stringent CR; VGPR, very good partial response.

Figure 2. IMWG (2016) response criteria for MM and new suggestion (continued)^1,2

abs., absolute; BM, bone marrow; CR, complete response; FLC, free light chain; IF, immunofixation; IMWG, International Myeloma Working Group; MR, minimal response; PC, plasma cell; PD, progressive disease; PR, partial response; (s)CR, stringent CR; SD. stable disease; VGPR, very good partial response.

The newly published suggestion for incorporation in the IMWG criteria states that a repeated BM biopsy for CR confirmation is unnecessary. This conclusion was drawn from a retrospective cohort study of 277 patients who underwent ASCT between 1998–2016. All included patients had pre-ASCT IF positivity and < 5% BM PCs, with a median PC level of 0.55% (range, 0.1–29). Following ASCT, 58% of patients remained IF positive in either serum or urine. A second BM biopsy was performed at a median of 3.3 months (range, 1.7–4.9) following ASCT.

In patients with post-ASCT IF negativity (serum and urine; n = 116):

• 98% had no difference in BM PC levels (< 5%)
• Two patients had a BM PC level of 7% and 15%, respectively (both had 6% clonal PCs)

In patients with post-ASCT IF positivity (n = 161):

• 94% had no difference in BM PC levels (< 5%)
• 8.7% had an increase in BM PC levels (median: 7.5%)
  • Twelve of them had detectable clonal PCs (median: 5.6%)

Discussion

The results of this prospective study indicate that there might be no need for a repeat BM biopsy after transplantation in order to confirm CR in patients who do not fulfil the IF criteria before transplantation. The authors hope to incorporate this new suggestion into the IMWG response criteria, since it would spare many patients with MM from painful and burdensome BM biopsies.

Limitations of the study include the exclusive evaluation of the CR response criteria and not for stringent CR, and the lack of imaging data on the status of soft tissue plasmacytomas pre- and post-ASCT.