The rules do not help us here, but only "interfere".
- Here «поэтому» is the introductory word
The adverb "поэтому" has a SPECIAL POSITION in this sentence, which is simply not considered in the rules. The word " поэтому "can be equated with the introductory word «следовательно» in all respects – both in meaning and in position at the beginning of the sentence before the interrogative pronoun "о чем". The logical stress falls on it, and it is highlighted by a pause:
ПоЭтому, //о чЁм тут может идти речь?
In other words, the actualization of the adverb is simply necessary here. The logical emphasis falls on both "поэтому" and the interrogative word "о чем". Can you read "поэтому о чем" without pausing between them? I don't think so.
- But you will not find evidence in the rules – this option is simply not considered in the classical code. But "поэтому" is included in the general list of words that are not introductory words, and you can point it out.
Do you want to refer to the rule on optional separation of circumstances? But even there you will not find any single adverb separated at the beginning of the sentence, although there is also no prohibition.
- In this way, there is a free zone without rules. You can't prove that a comma is necessary, but you can show the courage to put it. It is really needed here, and you have the right to author's punctuation. And you can refer to Rosenthal:
"If complete unification is desirable and necessary in the field of spelling, then this requirement does not apply to punctuation. The peculiarity of Russian punctuation is the flexibility of the punctuation system. All this excludes a formal approach to compliance with the rules."